Electron micrograph of a mitochondrion showing its mitochondrial matrix and membranes

In cell biology, a mitochondrion (plural mitochondria) is a membrane-enclosed organelle found in most eukaryotic cells. A micrograph, microphotograph or photomicrograph is a Photograph or similar image taken through a Microscope or similar device to show See also List of basic cell biology topics. Cell biology (also called cellular biology or formerly cytology, from the In Cell biology, an organelle (pronunciation /ɔː(rgəˡnɛl/ is a specialized subunit within a cell that has a specific function and is usually separately enclosed Animals Plants fungi, and Protists are eukaryotes (juːˈkærɪɒt or -oʊt Organisms whose cells are organized into complex The cell is the structural and functional unit of all known living Organisms It is the smallest unit of an organism that is classified as living and is often called ^[1] These organelles range from 1–10 micrometers (μm) in size. A micrometre ( American spelling: micrometer; symbol µm) is one millionth of a Metre, or equivalently one thousandth of a Millimetre Mitochondria are sometimes described as "cellular power plants" because they generate most of the cell's supply of adenosine triphosphate (ATP), used as a source of chemical energy. Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy In Physics and other Sciences energy (from the Greek grc ἐνέργεια - Energeia, "activity operation" from grc ἐνεργός In addition to supplying cellular energy, mitochondria are involved in a range of other processes, such as signaling, cellular differentiation, cell death, as well as the control of the cell cycle and cell growth. Cell signaling is part of a Complex system of Communication that governs basic cellular activities and coordinates cell actions In Developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized Cell type. The cell cycle, or cell-division cycle, is the series of events that take place in a eukaryotic cell leading to its replication The term cell growth is used in two different ways in Biology. ^[2] Mitochondria have been implicated in several human diseases, including mental disorders,^[3] cardiac dysfunction,^[4] and may play a role in the aging process. Mental disorder or mental illness is a psychological or behavioral pattern that occurs in an individual and is thought to cause distress or disability that is not expected as Ageing or aging (American English is the accumulation of changes in an organism The word mitochondrion comes from the Greek μίτος or mitos, thread + χονδρίον or khondrion, granule. Greek (el ελληνική γλώσσα or simply el ελληνικά — "Hellenic" is an Indo-European language, spoken today by 15-22 million people mainly Their ancestry is not fully understood, but, according to the endosymbiotic theory, mitochondria are descended from ancient bacteria, which were engulfed by the ancestors of eukaryotic cells more than a billion years ago. The endosymbiotic theory concerns the origins of mitochondria and Plastids (e The prokaryotes (proʊˈkærioʊts singular prokaryote /proʊˈkæriət/ are a group of Organisms that lack a Cell nucleus (= karyon or any other

Several characteristics make mitochondria unique. The number of mitochondria in a cell varies widely by organism and tissue type. Tissue is a cellular organizational level intermediate between cells and a complete organism Many cells have only a single mitochondrion, whereas others can contain several thousand mitochondria. ^[5][6] The organelle is composed of compartments that carry out specialized functions. These compartments or regions include the outer membrane, the intermembrane space, the inner membrane, and the cristae and matrix. The outer mitochondrial membrane, which encloses the entire organelle has a protein-to-phospholipid ratio similar to the eukaryotic plasma membrane (about 11 by weight The intermembrane space is the region between the Inner membrane and the Outer membrane of a Mitochondrion or a Chloroplast. The Mitochondrial inner membrane forms internal compartments known as Cristae which allow greater space for the proteins such as Cytochromes to function properly Cristae (singular crista) are the internal compartments formed by the inner membrane of a Mitochondrion. In the Mitochondrion, the matrix contains soluble Enzymes that catalyze the Oxidation of pyruvate and other small organic molecules Mitochondrial proteins vary depending on the tissues and species. In human, 615 distinct types of proteins were identified from cardiac mitochondria;^[7] whereas in murine, 940 proteins encoded by distinct genes were reported. Muridae is the largest family of Mammals It contains over 600 species found naturally throughout Eurasia Africa and Australia ^[8] Mitochondrial proteome is thought to be dynamically regulated. ^[9] Although most of a cell's DNA is contained in the cell nucleus, the mitochondrion has its own independent genome. In Cell biology, the nucleus (pl nuclei; from Latin la ''nucleus'' or la ''nuculeus'' "little nut" or kernel is a membrane-enclosed Mitochondrial DNA ( mtDNA) is the DNA located in Organelles called mitochondria. Further, its DNA shows substantial similarity to bacterial genomes. The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have In classical genetics the genome of a Diploid Organism including Eukarya refers to a full set of chromosomes or genes in a Gamete, thereby ^[10]

Structure

Simplified structure of mitochondrion

A mitochondrion contains inner and outer membranes composed of phospholipid bilayers and proteins. A lipid bilayer or bilayer lipid membrane ( BLM) is a membrane composed of Lipid molecules (usually Phospholipids. Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl ^[5] The two membranes, however, have different properties. Because of this double-membraned organization, there are five distinct compartments within the mitochondrion. There is the outer mitochondrial membrane, the intermembrane space (the space between the outer and inner membranes), the inner mitochondrial membrane, the cristae space (formed by infoldings of the inner membrane), and the matrix (space within the inner membrane). The outer mitochondrial membrane, which encloses the entire organelle has a protein-to-phospholipid ratio similar to the eukaryotic plasma membrane (about 11 by weight The intermembrane space is the region between the Inner membrane and the Outer membrane of a Mitochondrion or a Chloroplast. The Mitochondrial inner membrane forms internal compartments known as Cristae which allow greater space for the proteins such as Cytochromes to function properly Cristae (singular crista) are the internal compartments formed by the inner membrane of a Mitochondrion. In the Mitochondrion, the matrix contains soluble Enzymes that catalyze the Oxidation of pyruvate and other small organic molecules

Outer membrane

Main article: Outer mitochondrial membrane

The outer mitochondrial membrane, which encloses the entire organelle, has a protein-to-phospholipid ratio similar to that of the eukaryotic plasma membrane (about 1:1 by weight). The outer mitochondrial membrane, which encloses the entire organelle has a protein-to-phospholipid ratio similar to the eukaryotic plasma membrane (about 11 by weight In Cell biology, an organelle (pronunciation /ɔː(rgəˡnɛl/ is a specialized subunit within a cell that has a specific function and is usually separately enclosed Phospholipids are a class of Lipids and are a major component of all Biological membranes All phospholipids contain a Diglyceride, a Phosphate It contains large numbers of integral proteins called porins. An Integral Membrane Protein ( IMP) is a Protein Molecule (or assembly of proteins that is permanently attached to the Biological membrane. Porins are Beta barrel Proteins that cross a cellular membrane and act as a pore through which Molecules can diffuse. These porins form channels that allow molecules 5000 Daltons or less in molecular weight to freely diffuse from one side of the membrane to the other. The unified atomic mass unit ( u) or Dalton ( Da) or sometimes universal mass unit, is an unit of Mass used to express Diffusion is the net movement of particles (typically molecules from an area of high concentration to an area of low concentration by uncoordinated random movement ^[5] Larger proteins can also enter the mitochondrion if a signaling sequence at their N-terminus binds to a large multisubunit protein called translocase of the outer membrane, which then actively moves them across the membrane. The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or In Structural biology, a protein subunit or subunit protein is a single Protein Molecule that assembles (or " coassembles " The translocase of the outer membrane (TOM is a Protein found in the Outer mitochondrial membrane of the Mitochondria. ^[11] Disruption of the outer membrane permits proteins in the intermembrane space to leak into the cytosol, leading to certain cell death. ^[12]

Intermembrane space

The intermembrane space is the space between the outer membrane and the inner membrane. The intermembrane space is the region between the Inner membrane and the Outer membrane of a Mitochondrion or a Chloroplast. Because the outer membrane is freely permeable to small molecules, the concentrations of small molecules such as ions and sugars in the intermembrane space is the same as the cytosol. The cytosol or intracellular fluid (or cytoplasmic matrix) is the liquid found inside cells. ^[5] However, as large proteins must have a specific signaling sequence to be transported across the outer membrane, the protein composition of this space is different than the protein composition of the cytosol. The cytosol or intracellular fluid (or cytoplasmic matrix) is the liquid found inside cells. One protein that is localized to the intermembrane space in this way is cytochrome c. Cytochrome c, or cyt c (horse heart PDB 1HRC is a small Heme Protein found loosely associated with the inner membrane ^[12]

Inner membrane

Main article: Inner mitochondrial membrane

The inner mitochondrial membrane contains proteins with four types of functions:^[5]

1. Those that perform the redox reactions of oxidative phosphorylation
2. ATP synthase, which generates ATP in the matrix
3. Specific transport proteins that regulate metabolite passage into and out of the matrix
4. Protein import machinery. The Mitochondrial inner membrane forms internal compartments known as Cristae which allow greater space for the proteins such as Cytochromes to function properly Redox (shorthand for reduction-oxidation reaction describes all Chemical reactions in which atoms have their Oxidation number ( Oxidation state Oxidative phosphorylation is a Metabolic pathway that uses energy released by the oxidation of Nutrients to produce Adenosine triphosphate (ATP An ATP synthase ( is a general term for an Enzyme that can synthesize Adenosine triphosphate (ATP from Adenosine diphosphate (ADP and inorganic Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy Metabolomics is the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind" - specifically the study of their small-molecule metabolite

It contains more than 100 different polypeptides, and has a very high protein-to-phospholipid ratio (more than 3:1 by weight, which is about 1 protein for 15 phospholipids). Peptides (from the Greek πεπτίδια, "small digestibles" are short Polymers formed from the linking in a defined order of α- Amino The inner membrane is home to around 1/5 of the total protein in a mitochondrion. ^[5] In addition, the inner membrane is rich in an unusual phospholipid, cardiolipin. Cardiolipin (bis phosphatidyl Glycerol) is an important component of the inner Mitochondrial membrane, where it constitutes about 20% of the total lipid This phospholipid was originally discovered in beef hearts in 1942, and is usually characteristic of mitochondrial and bacterial plasma membranes. ^[13] Cardiolipin contains four fatty acids rather than two and may help to make the inner membrane impermeable. ^[5] Unlike the outer membrane, the inner membrane does not contain porins and is highly impermeable to all molecules. Almost all ions and molecules require special membrane transporters to enter or exit the matrix. Proteins are ferried into the matrix via the translocase of the inner membrane (TIM) complex or via Oxa1. ^[11] In addition, there is a membrane potential across the inner membrane formed by the action of the enzymes of the electron transport chain. An electron transport chain couples a chemical reaction between an electron donor (such as NADH) and an electron acceptor (such as O2) to the transfer

Cristae

Main article: crista

Cross-sectional image of cristae in rat liver mitochondrion to demonstrate the likely 3D structure and relationship to the inner membrane

The inner mitochondrial membrane is compartmentalized into numerous cristae, which expand the surface area of the inner mitochondrial membrane, enhancing its ability to produce ATP. Cristae (singular crista) are the internal compartments formed by the inner membrane of a Mitochondrion. Cristae (singular crista) are the internal compartments formed by the inner membrane of a Mitochondrion. These are not simple random folds but rather invaginations of the inner membrane, which can affect overall chemiosmotic function. Chemiosmosis is the diffusion of Ions across a selectively-permeable membrane ^[14] In typical liver mitochondria, for example, the surface area, including cristae, is about five times that of the outer membrane. The liver is a vital organ in the human body and is present in Vertebrates and some other animals Mitochondria of cells that have greater demand for ATP, such as muscle cells, contain more cristae than typical liver mitochondria. ^[5]

Matrix

Main article: mitochondrial matrix

The matrix is the space enclosed by the inner membrane. In the Mitochondrion, the matrix contains soluble Enzymes that catalyze the Oxidation of pyruvate and other small organic molecules It contains about 2/3 of the total protein in a mitochondrion. ^[5] The matrix is important in the production of ATP with the aid of the ATP synthase contained in the inner membrane. The matrix contains a highly-concentrated mixture of hundreds of enzymes, special mitochondrial ribosomes, tRNA, and several copies of the mitochondrial DNA genome. Ribosomes ( from ribo nucleic acid and "Greek soma ( meaning body") are complexes of RNA and Protein that Transfer RNA (abbreviated tRNA) is a small RNA (usually about 74-95 nucleotides that transfers a specific Amino acid to a growing polypeptide chain at Mitochondrial DNA ( mtDNA) is the DNA located in Organelles called mitochondria. In classical genetics the genome of a Diploid Organism including Eukarya refers to a full set of chromosomes or genes in a Gamete, thereby Of the enzymes, the major functions include oxidation of pyruvate and fatty acids, and the citric acid cycle. Pyruvic acid (CH3COCO2H is an alpha-keto acid. The Carboxylate Anion of pyruvic acid is known as pyruvate. In Chemistry, especially Biochemistry, a fatty acid is a Carboxylic acid often with a long unbranched Aliphatic tail ( chain) which The citric acid cycle, also known as the tricarboxylic acid cycle ( TCA cycle) or the Krebs cycle, (or rarely the Szent-Györgyi–Krebs cycle ^[5]

Mitochondria have their own genetic material, and the machinery to manufacture their own RNAs and proteins (see: protein biosynthesis). Ribonucleic acid ( RNA) is a Nucleic acid that consists of a long chain of Nucleotide units Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl Protein biosynthesis (synthesis is the process in which cells build Proteins The term is sometimes used to refer only to protein translation but more A published human mitochondrial DNA sequence revealed 16,569 base pairs encoding 37 total genes, 24 tRNA and rRNA genes and 13 peptide genes. In Molecular biology, two Nucleotides on opposite complementary DNA or RNA strands that are connected via Hydrogen bonds are called Transfer RNA (abbreviated tRNA) is a small RNA (usually about 74-95 nucleotides that transfers a specific Amino acid to a growing polypeptide chain at Ribosomal RNA ( rRNA) is the central component of the Ribosome, the protein manufacturing machinery of all living cells. Peptides (from the Greek πεπτίδια, "small digestibles" are short Polymers formed from the linking in a defined order of α- Amino ^[15] The 13 mitochondrial peptides in humans are integrated into the inner mitochondrial membrane, along with proteins encoded by genes that reside in the host cell's nucleus. Peptides (from the Greek πεπτίδια, "small digestibles" are short Polymers formed from the linking in a defined order of α- Amino Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance In Cell biology, the nucleus (pl nuclei; from Latin la ''nucleus'' or la ''nuculeus'' "little nut" or kernel is a membrane-enclosed

Organization and distribution

Mitochondria are found in nearly all eukaryotes. Animals Plants fungi, and Protists are eukaryotes (juːˈkærɪɒt or -oʊt Organisms whose cells are organized into complex They vary in number and location according to cell type. Substantial numbers of mitochondria are in the liver, with about 1000–2000 mitochondria per cell making up 1/5th of the cell volume. ^[5] The mitochondria can be found nestled between myofibrils of muscle or wrapped around the sperm flagellum. Myofibrils (obsolete term sarcostyles) are cylindrical Organelles found within Muscle cells They are bundles of actomyosin filaments Muscle (from Latin musculus, diminutive of mus "mouse" is contractile tissue of the body and is derived from the The term sperm is derived from the Greek word (σπέρμα sperma (meaning "seed" and refers to the male reproductive cells. A flagellum ( plural flagella) is a tail-like structure that projects from the Cell body of certain Prokaryotic and Eukaryotic cells and it ^[5] Often they form a complex 3D branching network inside the cell with the cytoskeleton. cytoskeleton (also CSK is a cellular " Scaffolding " or " Skeleton " contained within the Cytoplasm. The association with the cytoskeleton determines mitochondrial shape, which can affect the function as well. ^[16] Recent evidence suggests vimentin, one of the components of the cytoskeleton, is critical to the association with the cytoskeleton. Vimentin is a member of the Intermediate filament family of proteins ^[17]

Function

The most prominent roles of the mitochondrion are its production of ATP and regulation of cellular metabolism. Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy Metabolism is the set of Chemical reactions that occur in living Organisms in order to maintain Life. ^[6] The central set of reactions involved in ATP production are collectively known as the citric acid cycle. The citric acid cycle, also known as the tricarboxylic acid cycle ( TCA cycle) or the Krebs cycle, (or rarely the Szent-Györgyi–Krebs cycle However, the mitochondrion has many other functions in addition to the production of ATP.

Energy conversion

A dominant role for the mitochondria is the production of ATP, as reflected by the large number of proteins in the inner membrane for this task. Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy This is done by oxidizing the major products of glucose, pyruvate, and NADH, which are produced in the cytosol. Glucose (Glc a Monosaccharide (or simple Sugar) also known as grape sugar, is an important Carbohydrate in Biology. Pyruvic acid (CH3COCO2H is an alpha-keto acid. The Carboxylate Anion of pyruvic acid is known as pyruvate. Nicotinamide adenine dinucleotide, abbreviated NAD+, is a Coenzyme found in all living cells The compound is a dinucleotide since it consists ^[6] This process of cellular respiration, also known as aerobic respiration, is dependent on the presence of oxygen. Cellular respiration is the set of the metabolic reactions and processes that take place in Organisms cells to convert biochemical energy from Cellular respiration is the set of the metabolic reactions and processes that take place in Organisms cells to convert biochemical energy from Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the When oxygen is limited, the glycolytic products will be metabolized by anaerobic respiration, a process that is independent of the mitochondria. See also Fermentation (biochemistry Anaerobic respiration (anaerobiosis refers to the Oxidation of molecules in the absence of Oxygen to produce ^[6] The production of ATP from glucose has an approximately 13-fold higher yield during aerobic respiration compared to anaerobic respiration. ^[18]

Pyruvate: the citric acid cycle

Main articles: pyruvate decarboxylation and citric acid cycle

Each pyruvate molecule produced by glycolysis is actively transported across the inner mitochondrial membrane, and into the matrix where it is oxidized and combined with coenzyme A to form CO₂, acetyl-CoA, and NADH. Pyruvate decarboxylation is the biochemical reaction that uses Pyruvate to form Acetyl-CoA, releasing reducing equivalents and Carbon dioxide. The citric acid cycle, also known as the tricarboxylic acid cycle ( TCA cycle) or the Krebs cycle, (or rarely the Szent-Györgyi–Krebs cycle Active transport is the mediated process of moving particles across Biological membrane against the concentration gradient Beta oxidation is the process by which Fatty acids in the form of Acyl-CoA molecules are broken down in Mitochondria and/or in Peroxisomes to Coenzyme A ( CoA, CoASH, or HSCoA) is a Coenzyme, notable for its role in the synthesis and oxidation of Fatty acids Acetyl-CoA is an important molecule in metabolism used in many biochemical reactions Nicotinamide adenine dinucleotide, abbreviated NAD+, is a Coenzyme found in all living cells The compound is a dinucleotide since it consists ^[6]

The acetyl-CoA is the primary substrate to enter the citric acid cycle, also known as the tricarboxylic acid (TCA) cycle or Krebs cycle. The citric acid cycle, also known as the tricarboxylic acid cycle ( TCA cycle) or the Krebs cycle, (or rarely the Szent-Györgyi–Krebs cycle The enzymes of the citric acid cycle are located in the mitochondrial matrix, with the exception of succinate dehydrogenase, which is bound to the inner mitochondrial membrane as part of Complex II. Succinate-coenzyme Q reductase ( EC 1351; succinate dehydrogenase) is an Enzyme complex bound to the inner Mitochondrial membrane ^[19] The citric acid cycle oxidizes the acetyl-CoA to carbon dioxide, and, in the process, produces reduced cofactors (three molecules of NADH and one molecule of FADH₂) that are a source of electrons for the electron transport chain, and a molecule of GTP (that is readily converted to an ATP). Nicotinamide adenine dinucleotide, abbreviated NAD+, is a Coenzyme found in all living cells The compound is a dinucleotide since it consists In Biochemistry, flavin adenine dinucleotide ( FAD) is a Redox cofactor involved in several important reactions in Metabolism. An electron transport chain couples a chemical reaction between an electron donor (such as NADH) and an electron acceptor (such as O2) to the transfer Guanosine-5'-triphosphate ( GTP) is a Purine Nucleotide. One role is as substrate for the synthesis of RNA during transcription. ^[6]

NADH and FADH₂: the electron transport chain

Main articles: Electron transport chain and Oxidative phosphorylation

Schematic of typical animal cell, showing subcellular components. An electron transport chain couples a chemical reaction between an electron donor (such as NADH) and an electron acceptor (such as O2) to the transfer Oxidative phosphorylation is a Metabolic pathway that uses energy released by the oxidation of Nutrients to produce Adenosine triphosphate (ATP Organelles:
(1) nucleolus
(2) nucleus
(3) ribosomes (little dots)
(4) vesicle
(5) rough endoplasmic reticulum (ER)
(6) Golgi apparatus
(7) Cytoskeleton
(8) smooth ER
(9) mitochondria
(10) vacuole
(11) cytoplasm
(12) lysosome
(13) centrioles within centrosome

The redox energy from NADH and FADH₂ is transferred to oxygen (O₂) in several steps via the electron transport chain. In Cell biology, an organelle (pronunciation /ɔː(rgəˡnɛl/ is a specialized subunit within a cell that has a specific function and is usually separately enclosed The nucleolus (also called nucleole) is a structure found within the nucleus in which Ribosomal RNA is transcribed. In Cell biology, the nucleus (pl nuclei; from Latin la ''nucleus'' or la ''nuculeus'' "little nut" or kernel is a membrane-enclosed A vesicle is a small bubble of liquid within a cell A more formal definition in Cell biology, would be that a vesicle is a relatively small intracellular membrane-enclosed The endoplasmic reticulum (Greek endo = "within" (prefix plásma = "formed entity" Latin reticulum = "little net" or ER, is an Organelle The Golgi apparatus (also called the cytoskeleton (also CSK is a cellular " Scaffolding " or " Skeleton " contained within the Cytoplasm. In general vacuole functions include Removing unwanted structural debris Isolating materials that might be harmful or a threat to the cell Containing The cytoplasm is the contents of a cell that is enclosed within the Plasma membrane. Lysosomes are Organelles that contain Digestive enzymes (acid Hydrolases. A Centriole is a barrel shaped Organelle found in most animal Eukaryotic cells though absent in Higher plants and Fungi. In Cell biology, the centrosome is an Organelle that serves as the main Microtubule organizing center (MTOC of the animal cell as well These energy-rich molecules are produced within the matrix via the citric acid cycle but are also produced in the cytoplasm by glycolysis. See also Gluconeogenesis, which carries out a process wherein glucose is synthesized rather than catabolized Reducing equivalents from the cytoplasm can be imported via the malate-aspartate shuttle system of antiporter proteins or feed into the electron transport chain using a glycerol phosphate shuttle. The malate-aspartate shuttle (sometimes also the malate shuttle) is a biochemical system for translocating electrons produced during Glycolysis (TCA/Krebs Cycle across An antiporter (also called exchanger or counter-transporter) is an Integral membrane protein which is involved in Secondary active transport The glycerol-3-phosphate shuttle is a mechanism that regenerates NAD+ from NADH, a by-product of Glycolysis. ^[6] Protein complexes in the inner membrane (NADH dehydrogenase, cytochrome c reductase, and cytochrome c oxidase) perform the transfer and the incremental release of energy is used to pump protons (H⁺) into the intermembrane space. An electron transport chain couples a chemical reaction between an electron donor (such as NADH) and an electron acceptor (such as O2) to the transfer NADH dehydrogenase ( is an Enzyme located in the inner mitochondrial membrane that catalyzes the transfer of Electrons from NADH to Coenzyme The coenzyme Q: cytochrome c — oxidoreductase, sometimes called the cytochrome bc 1 complex, and at other times complex III The Enzyme cytochrome c oxidase or Complex IV () is a large Transmembrane protein complex found in Bacteria and the Mitochondrion Hydrogen ion is recommended by IUPAC as a general term for all Ions of Hydrogen and its Isotopes Depending on the Charge of the ion This process is efficient, but a small percentage of electrons may prematurely reduce oxygen, forming reactive oxygen species such as superoxide. Reactive oxygen species (ROS are ions or very small molecules that include Oxygen Ions free radicals, and Peroxides both inorganic and Superoxide is the Anion O2&minus It is important as the product of the one-electron reduction of Dioxygen, which occurs widely in nature ^[6] This can cause oxidative stress in the mitochondria and may contribute to the decline in mitochondrial function associated with the aging process. Oxidative stress is caused by an imbalance between the production of reactive oxygen and a biological system's ability to readily detoxify the reactive intermediates or easily ^[20]

As the proton concentration increases in the intermembrane space, a strong electrochemical gradient is established across the inner membrane. In Cellular biology, an electrochemical gradient is a spatial variation of both Electrical potential and chemical Concentration across a membrane The protons can return to the matrix through the ATP synthase complex, and their potential energy is used to synthesize ATP from ADP and inorganic phosphate (P_i). An ATP synthase ( is a general term for an Enzyme that can synthesize Adenosine triphosphate (ATP from Adenosine diphosphate (ADP and inorganic Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy ^[6] This process is called chemiosmosis, and was first described by Peter Mitchell^[21][22] who was awarded the 1978 Nobel Prize in Chemistry for his work. Chemiosmosis is the diffusion of Ions across a selectively-permeable membrane Peter Dennis Mitchell ( September 29 1920 &ndash April 10 1992) was a British biochemist who was awarded the 1978 Nobel Prize for Chemistry The Nobel Prize in Chemistry (Nobelpriset i kemi is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of Chemistry. Later, part of the 1997 Nobel Prize in Chemistry was awarded to Paul D. Boyer and John E. Walker for their clarification of the working mechanism of ATP synthase. Paul Delos Boyer (born July 31, 1918) is an American Biochemist. John Ernest Walker (born January 7, 1941) is an English chemist who won the Nobel Prize in Chemistry in 1997 ^[23]

Heat production

Under certain conditions, protons can re-enter the mitochondrial matrix without contributing to ATP synthesis. This process is known as proton leak or mitochondrial uncoupling and is due to the facilitated diffusion of protons into the matrix. Facilitated diffusion (or facilitated transport) is a process of Diffusion, a form of Passive transport facilitated by Transport proteins The The process results in the unharnessed potential energy of the proton electrochemical gradient being released as heat. ^[6] The process is mediated by a proton channel called thermogenin, or UCP1. Thermogenin (called Uncoupling protein by its discoverers and now known as uncoupling protein 1 or UCP1) is an uncoupling protein found in the mitochondria Thermogenin (called Uncoupling protein by its discoverers and now known as uncoupling protein 1 or UCP1) is an uncoupling protein found in the mitochondria ^[24] Thermogenin is a 33kDa protein first discovered in 1973. The unified atomic mass unit ( u) or Dalton ( Da) or sometimes universal mass unit, is an unit of Mass used to express ^[25] Thermogenin is primarily found in brown adipose tissue, or brown fat, and is responsible for non-shivering thermogenesis. Brown adipose tissue ( BAT) or brown fat is one of the two types of Adipose tissue (the other being White adipose tissue) that is present in many Brown adipose tissue is found in mammals, and is at its highest levels in early life and in hibernating animals. In humans, brown adipose tissue is present at birth and decreases with age. ^[24]

Storage of calcium ions

The concentrations of free calcium in the cell can regulate an array of reactions and is important for signal transduction in the cell. Calcium (Ca2+ plays a vital role in the Anatomy, Physiology and Biochemistry of Organisms and of the cell, particularly Mitochondria can transiently store calcium, a contributing process for the cell's homeostasis of calcium. Calcium (Ca2+) storages (in Cell biology) are Intracellular Organelles that constantly accumulate Ca2+ ions and release ^[26] In fact, their ability to rapidly take in calcium for later release makes them very good "cytosolic buffers" for calcium. ^[27] The endoplasmic reticulum (ER) is the most significant storage site of calcium, and there is a significant interplay between the mitochondrion and ER with regard to calcium. The endoplasmic reticulum (Greek endo = "within" (prefix plásma = "formed entity" Latin reticulum = "little net" or ER, is an Organelle ^[28] The calcium is taken up into the matrix by a calcium uniporter on the inner mitochondrial membrane. In the Mitochondrion, the matrix contains soluble Enzymes that catalyze the Oxidation of pyruvate and other small organic molecules A uniporter is an Integral membrane protein that is involved in Facilitated diffusion. The Mitochondrial inner membrane forms internal compartments known as Cristae which allow greater space for the proteins such as Cytochromes to function properly ^[29] It is primarily driven by the mitochondrial membrane potential. Membrane potential (or transmembrane potential) is the Voltage difference (or Electrical potential difference between the interior and exterior of a ^[26] Release of this calcium back into the cell's interior can occur via a sodium-calcium exchange protein or via "calcium-induced-calcium-release" pathways. ^[29] This can initiate calcium spikes or calcium waves with large changes in the membrane potential. Membrane potential (or transmembrane potential) is the Voltage difference (or Electrical potential difference between the interior and exterior of a These can activate a series of second messenger system proteins that can coordinate processes such as neurotransmitter release in nerve cells and release of hormones in endocrine cells. In Cell physiology, a secondary messenger system (also known as a second messenger system) is a method of cellular signaling whereby a diffusable signaling molecule In a Neuron, synaptic vesicles, also called neurotransmitter vesicles, store the various Neurotransmitters that are released during Calcium -regulated Hormones (from Greek ὁρμή - "impetus" are chemicals released by cells that affect cells in other parts of the body

Additional functions

Mitochondria play a central role in many other metabolic tasks, such as:

• Regulation of the membrane potential^[6]
• Apoptosis-programmed cell death^[30]
• Glutamate-mediated excitotoxic neuronal injury^[31]
• Cellular proliferation regulation^[32]
• Regulation of cellular metabolism^[32]
• Certain heme synthesis reactions^[33] (see also: porphyrin)
• Steroid synthesis. Metabolism is the set of Chemical reactions that occur in living Organisms in order to maintain Life. Membrane potential (or transmembrane potential) is the Voltage difference (or Electrical potential difference between the interior and exterior of a Glutamic acid (abbreviated as Glu or E) is one of the 20 Alpha Amino acids It is not among the human Essential amino acids Its Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information Metabolism is the set of Chemical reactions that occur in living Organisms in order to maintain Life. A heme ( American English) or haem ( British English) is a Prosthetic group that consists of an Iron atom contained in the center of A porphyrin is a heterocyclic Macrocycle derived from four Pyrroline subunits interconnected via their α carbon atoms via Methine bridges (=CH- A steroid is a Terpenoid Lipid characterized by a Carbon skeleton with four fused rings generally arranged in a 6-6-6-5 fashion ^[27]

Some mitochondrial functions are performed only in specific types of cells. For example, mitochondria in liver cells contain enzymes that allow them to detoxify ammonia, a waste product of protein metabolism. The liver is a vital organ in the human body and is present in Vertebrates and some other animals Ammonia is a compound with the formula N[[hydrogen H3]] It is normally encountered as a Gas with a characteristic pungent Odor A mutation in the genes regulating any of these functions can result in mitochondrial diseases. Mitochondrial diseases are a group of disorders relating to the mitochondria, the Organelles that are the "powerhouses" of the eukaryotic cells

Origin

Main article: Endosymbiotic theory

Mitochondria have many features in common with prokaryotes. The endosymbiotic theory concerns the origins of mitochondria and Plastids (e The prokaryotes (proʊˈkærioʊts singular prokaryote /proʊˈkæriət/ are a group of Organisms that lack a Cell nucleus (= karyon or any other As a result, they are believed to be originally derived from endosymbiotic prokaryotes. An endosymbiont is any Organism that lives within the body or cells of another organism i

Mitochondria contain DNA which is formed only during the division of other mitochondria within the cell. Mitochondrial DNA ( mtDNA) is the DNA located in Organelles called mitochondria. This DNA contains genes for ribosomes, and the twenty-one tRNA's necessary for the translation of messenger RNAs into protein. Ribosomes ( from ribo nucleic acid and "Greek soma ( meaning body") are complexes of RNA and Protein that Transfer RNA (abbreviated tRNA) is a small RNA (usually about 74-95 nucleotides that transfers a specific Amino acid to a growing polypeptide chain at Messenger ribonucleic acid ( mRNA) is a molecule of RNA encoding a chemical "blueprint" for a Protein product The DNA is often circular, as is most bacterial DNA, and employs a variant genetic code similar to that of Proteobacteria. The genetic code is the set of rules by which information encoded in genetic material ( DNA or RNA sequences is translated into Proteins The Proteobacteria are a major group ( Phylum) of Bacteria. They include a wide variety of Pathogens such as Escherichia, ^[34] This suggests that their ancestor, the so-called proto-mitochondrion, was a member of the Proteobacteria. The proto-mitochondrion is the ancestral bacterial Endosymbiont from which all Mitochondria are thought to be derived The Proteobacteria are a major group ( Phylum) of Bacteria. They include a wide variety of Pathogens such as Escherichia, ^[35] In particular, the proto-mitochondrion was probably related to the rickettsia. The Rickettsiales, also called rickettsias are an order of small Proteobacteria. ^[36] However, the exact relationship of the ancestor of mitochondria to the alpha-proteobacteria and whether the mitochondria was formed at the same time or after the nucleus, remains controversial. ^[37]

The ribosomes coded for by the mitochondrial DNA are similar to those from bacteria in size and structure. ^[38] They closely resemble the bacterial 70S ribosome and not the 80S cytoplasmic ribosomes which are coded for by nuclear DNA. Ribosomes ( from ribo nucleic acid and "Greek soma ( meaning body") are complexes of RNA and Protein that Ribosomes ( from ribo nucleic acid and "Greek soma ( meaning body") are complexes of RNA and Protein that The cytoplasm is the contents of a cell that is enclosed within the Plasma membrane. In Cell biology, the nucleus (pl nuclei; from Latin la ''nucleus'' or la ''nuculeus'' "little nut" or kernel is a membrane-enclosed

The endosymbiotic relationship of mitochondria with their host cells was popularized by Lynn Margulis. An endosymbiont is any Organism that lives within the body or cells of another organism i Lynn Margulis (born March 5, 1938) is an American Biologist and University Professor in the Department of Geosciences ^[39] The endosymbiotic hypothesis suggests that mitochondria descended from bacteria that somehow survived endocytosis by another cell, and became incorporated into the cytoplasm. The endosymbiotic theory concerns the origins of mitochondria and Plastids (e Endocytosis is a process where cells absorb material ( Molecules such as proteins from the outside by engulfing it with their Cell membrane. The cytoplasm is the contents of a cell that is enclosed within the Plasma membrane. The ability of these bacteria to conduct respiration in host cells that had relied on glycolysis and fermentation would have provided a considerable evolutionary advantage. See also Gluconeogenesis, which carries out a process wherein glucose is synthesized rather than catabolized In a similar manner, host cells with symbiotic bacteria capable of photosynthesis would also have had an advantage. Photosynthesis is a Metabolic pathway that converts Light Energy into Chemical energy. The incorporation of symbiotes would have increased the number of environments in which the cells could survive. This symbiotic relationship probably developed 1. 7^[40]-2^[41] billion years ago.

A few groups of unicellular eukaryotes lack mitochondria: the microsporidians, metamonads, and archamoebae. Microsporidia are parasites of animals now considered to be extremely reduced fungi. The metamonads are a large group of Flagellate protozoa Their composition is not entirely settled but they include the Retortamonads Diplomonads and The Archamoebae are a group of Amoebozoa distinguished by the absence of mitochondria. ^[42] These groups appear as the most primitive eukaryotes on phylogenetic trees constructed using rRNA information, suggesting that they appeared before the origin of mitochondria. A phylogenetic tree, also called an evolutionary tree, is a tree showing the Evolutionary relationships among various biological Species or other Ribosomal RNA ( rRNA) is the central component of the Ribosome, the protein manufacturing machinery of all living cells. However, this is now known to be an artifact of long-branch attraction – they are derived groups and retain genes or organelles derived from mitochondria (e. Long branch attraction (LBA is a phenomenon in Phylogenetic analyses (most commonly those employing Maximum parsimony) when rapidly evolving lineages are inferred g. , mitosomes and hydrogenosomes). A mitosome is an Organelle found in some unicellular eukaryotic organisms A hydrogenosome is a membrane-enclosed Organelle of some anaerobic Ciliates trichomonads and Fungi. ^[1]

Genome

Main article: Mitochondrial DNA

The human mitochondrial genome is a circular DNA molecule of about 16 kilobases. Mitochondrial DNA ( mtDNA) is the DNA located in Organelles called mitochondria. Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known In Molecular biology, two Nucleotides on opposite complementary DNA or RNA strands that are connected via Hydrogen bonds are called ^[43] It encodes 37 genes: 13 for subunits of respiratory complexes I, III, IV, and V, 22 for mitochondrial tRNA, and 2 for rRNA. In Structural biology, a protein subunit or subunit protein is a single Protein Molecule that assembles (or " coassembles " Transfer RNA (abbreviated tRNA) is a small RNA (usually about 74-95 nucleotides that transfers a specific Amino acid to a growing polypeptide chain at Ribosomal RNA ( rRNA) is the central component of the Ribosome, the protein manufacturing machinery of all living cells. ^[43] One mitochondrion can contain two to ten copies of its DNA. ^[44]

As in prokaryotes, there is a very high proportion of coding DNA and an absence of repeats. Mitochondrial genes are transcribed as multigenic transcripts, which are cleaved and polyadenylated to yield mature mRNAs. Transcription is the synthesis of RNA under the direction of DNA Polyadenylation is the synthesis of a poly(A tail a stretch of RNA where all the bases are Adenines at the end of an RNA molecule Messenger ribonucleic acid ( mRNA) is a molecule of RNA encoding a chemical "blueprint" for a Protein product Not all proteins necessary for mitochondrial function are encoded by the mitochondrial genome; most are coded by genes in the cell nucleus and the corresponding proteins imported into the mitochondrion. In Cell biology, the nucleus (pl nuclei; from Latin la ''nucleus'' or la ''nuculeus'' "little nut" or kernel is a membrane-enclosed ^[45] The exact number of genes encoded by the nucleus and the mitochondrial genome differs between species. Mitochondrial DNA ( mtDNA) is the DNA located in Organelles called mitochondria. In general, mitochondrial genomes are circular, although exceptions have been reported. ^[46] Also, in general, mitochondrial DNA lacks introns, as is the case in the human mitochondrial genome;^[45] however, introns have been observed in some eukaryotic mitochondrial DNA,^[47] such as that of yeast^[48] and protists,^[49] including Dictyostelium discoideum. Introns, derived from the term "intragenic regions" and also called intervening sequence (IVS are DNA regions in a Gene that are not translated into Yeasts are a growth form of eukaryotic Microorganisms classified in the kingdom Fungi, with about 1500 Species currently described Protists (ˈproʊtɨst are a diverse group of eukaryotic Microorganisms Historically protists were treated as the kingdom Protista but this The dictyostelids are a group of cellular Slime molds or social Amoebae When food (normally bacteria is readily available they take the form of individual amoebae ^[50]

While slight variations on the standard code had been predicted earlier,^[51] none was discovered until 1979, when researchers studying human mitochondrial genes determined that they used an alternative code. Mitochondrial genetics is the study of the Genetics of the DNA contained in Mitochondria. ^[52] Many slight variants have been discovered since,^[53] including various alternative mitochondrial codes. ^[54] Further, the AUA, AUC, and AUU codons are all allowable start codons.

Some of these differences should be regarded as pseudo-changes in the genetic code due to the phenomenon of RNA editing, which is common in mitochondria. The term RNA editing describes those molecular processes in which the information content in an RNA molecule is altered through a chemical change in the base makeup In higher plants, it was thought that CGG encoded for tryptophan and not arginine; however, the codon in the processed RNA was discovered to be the UGG codon, consistent with the universal genetic code for tryptophan. Tryptophan (abbreviated as Trp or W) is one of the 20 standard amino acids, as well as an Essential amino acid in the Human diet Arginine (abbreviated as Arg or R) is an α- Amino acid. The L-form is one of the 20 most common natural amino acids The genetic code is the set of rules by which information encoded in genetic material ( DNA or RNA sequences is translated into Proteins ^[55] Of note, the arthropod mitochondrial genetic code has undergone parallel evolution within a phylum, with some organisms uniquely translating AGG to lysine. ^[56]

Mitochondrial genomes have far fewer genes than the eubacteria from which they are thought to be descended. The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have Although some have been lost altogether, many have been transferred to the nucleus, such as the respiratory complex II protein subunits. In Cell biology, the nucleus (pl nuclei; from Latin la ''nucleus'' or la ''nuculeus'' "little nut" or kernel is a membrane-enclosed ^[43] This is thought to be relatively common over evolutionary time. A few organisms, such as the Cryptosporidium, actually have mitochondria that lack any DNA, presumably because all their genes have been lost or transferred. Cryptosporidium is a Protozoan that can cause gastro-intestinal illness with Diarrhea in humans ^[57] In Cryptosporidium, the mitochondria have an altered ATP generation system that renders the parasite resistant to many classical mitochondrial inhibitors such as cyanide, azide, and atovaquone. Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy A cyanide is any Chemical compound that contains the cyano group (C≡N which consists of a Carbon Atom triple-bonded to a Azide is the anion with the formula N3− It is the Conjugate base of Hydrazoic acid. Atovaquone (alternative spelling atavaquone) is a chemical compound that belongs to the class of Naphthalenes Atovaquone is a hydroxy-14-naphthoquinone an analog ^[57]

Replication and inheritance

See also: mitochondrial genome

Mitochondria divide by binary fission similar to bacterial cell division; unlike bacteria, however, mitochondria can also fuse with other mitochondria. The mitochondrial genome is the genetic material of the Mitochondria. Binary fission is the form of Asexual reproduction and Cell division used by Prokaryotic organisms (such as Bacteria or Archea) ^[43][58]. The regulation of this division differs between eukaryotes. In many single-celled eukaryotes, their growth and division is linked to the cell cycle. The cell cycle, or cell-division cycle, is the series of events that take place in a eukaryotic cell leading to its replication For example, a single mitochondrion may divide synchronously with the nucleus. This division and segregation process must be tightly controlled so that each daughter cell receives at least one mitochondrion. In other eukaryotes (in humans for example), mitochondria may replicate their DNA and divide mainly in response to the energy needs of the cell, rather than in phase with the cell cycle. When the energy needs of a cell are high, mitochondria grow and divide. When the energy use is low, mitochondria are destroyed or become inactive. In such examples, and in contrast to the situation in many single celled eukaryotes, mitochondria are apparently randomly distributed to the daughter cells during the division of the cytoplasm. The cytoplasm is the contents of a cell that is enclosed within the Plasma membrane.

Mitochondrial genes are not inherited by the same mechanism as nuclear genes. At fertilization of an egg cell by a sperm, the egg nucleus and sperm nucleus each contribute equally to the genetic makeup of the zygote nucleus. An ovum (plural ova) is a Haploid Female reproductive cell or Gamete. For other meanings see Zygote (disambiguation. A zygote (from Greek ζυγωτός zugōtos "joined" or "yoked" In contrast, the mitochondria, and therefore the mitochondrial DNA, usually comes from the egg only. The sperm's mitochondria enters the egg but does not contribute genetic information to the embryo. ^[59] Instead, paternal mitochondria are marked with ubiquitin to select them for later destruction inside the embryo. Ubiquitin is a highly-conserved regulatory Protein that is ''ubiquitously'' expressed in Eukaryotes. An embryo (from Greek:, plural, lit "that which grows" from en- "in" + bryein "to swell be full" is a multicellular ^[60] The egg cell contains relatively few mitochondria, but it is these mitochondria that survive and divide to populate the cells of the adult organism. Mitochondria are, therefore, in most cases inherited down the female line, known as maternal inheritance. Non-Mendelian inheritance is a general term that refers to any pattern of inheritance in which traits do not segregate in accordance with Mendel’s laws This mode is seen in most organisms including all animals. However, mitochondria in some species can sometimes be inherited paternally. This is the norm among certain coniferous plants, although not in pine trees and yew trees. This article is about the tree For other uses of the term "pine" see Pine (disambiguation. ^[61] It has also been suggested that it occurs at a very low level in humans. ^[62]

Uniparental inheritance leads to little opportunity for genetic recombination between different lineages of mitochondria, although a single mitochondrion can contain 2–10 copies of its DNA. Genetic recombination is the process by which a strand of genetic material (usually DNA; but can also be RNA) is broken and then joined to a different DNA molecule ^[44] For this reason, mitochondrial DNA usually is thought to reproduce by binary fission. Binary fission is the form of Asexual reproduction and Cell division used by Prokaryotic organisms (such as Bacteria or Archea) What recombination does take place maintains genetic integrity rather than maintaining diversity. However, there are studies showing evidence of recombination in mitochondrial DNA. It is clear that the enzymes necessary for recombination are present in mammalian cells. ^[63] Further, evidence suggests that animal mitochondria can undergo recombination. ^[64] The data are a bit more controversial in humans, although indirect evidence of recombination exists. ^[65][66] If recombination does not occur, the whole mitochondrial DNA sequence represents a single haplotype, which makes it useful for studying the evolutionary history of populations. The term haplotype is a contraction of the term " haploid Genotype.

Population genetic studies

Main article: Human mitochondrial genetics

The near-absence of genetic recombination in mitochondrial DNA makes it a useful source of information for scientists involved in population genetics and evolutionary biology. Mitochondrial genetics is the study of the Genetics of the DNA contained in Mitochondria. Genetic recombination is the process by which a strand of genetic material (usually DNA; but can also be RNA) is broken and then joined to a different DNA molecule Population genetics is the study of the Allele frequency distribution and change under the influence of the four evolutionary forces Natural selection, Genetic Evolutionary biology is a sub-field of Biology concerned with the origin of Species from a Common descent, and Descent of species ^[67] Because all the mitochondrial DNA is inherited as a single unit, or haplotype, the relationships between mitochondrial DNA from different individuals can be represented as a gene tree. The term haplotype is a contraction of the term " haploid Genotype. A phylogenetic tree, also called an evolutionary tree, is a tree showing the Evolutionary relationships among various biological Species or other Patterns in these gene trees can be used to infer the evolutionary history of populations. The classic example of this is in human evolutionary genetics, where the molecular clock can be used to provide a recent date for mitochondrial Eve. The molecular clock (based on the molecular clock hypothesis ( MCH) is a technique in Molecular evolution to relate the divergence time of two Species Mitochondrial Eve ( mt-mrca) is the name given by researchers to the woman who is defined as the Matrilineal most recent common ancestor (MRCA for all currently ^[68][69] This is often interpreted as strong support for a recent modern human expansion out of Africa. In Paleoanthropology, the recent African origin of modern humans is one of two hypotheses of the origin of anatomically modern humans Homo sapiens sapiens ^[70] Another human example is the sequencing of mitochondrial DNA from Neanderthal bones. The Neanderthal (neɪˈændərtɑːl also with /niː-/ and /-θɔːl/ or Neandertal, is an extinct member of the Homo genus that is known from The relatively-large evolutionary distance between the mitochondrial DNA sequences of Neanderthals and living humans has been interpreted as evidence for lack of interbreeding between Neanderthals and anatomically-modern humans. ^[71]

However, mitochondrial DNA reflects the history of only females in a population and so may not represent the history of the population as a whole. This can be partially overcome by the use of paternal genetic sequences, such as the non-recombining region of the Y-chromosome. Genetic recombination is the process by which a strand of genetic material (usually DNA; but can also be RNA) is broken and then joined to a different DNA molecule The Y chromosome is the sex-determining Chromosome in most Mammals including Humans In mammals it contains the gene SRY, which triggers ^[70] In a broader sense, only studies that also include nuclear DNA can provide a comprehensive evolutionary history of a population. Nuclear DNA, nuclear deoxyribonucleic acid (nDNA is DNA contained within a nucleus of eukaryotic organisms. ^[72]

Dysfunction and disease

Mitochondrial diseases

Main article: Mitochondrial disease

With their central place in cell metabolism, damage - and subsequent dysfunction - in mitochondria is an important factor in a wide range of human diseases. Mitochondrial diseases are a group of disorders relating to the mitochondria, the Organelles that are the "powerhouses" of the eukaryotic cells Mitochondrial disorders often present as neurological disorders, but can manifest as myopathy, diabetes, multiple endocrinopathy, or a variety of other systemic manifestations. In Medicine, a myopathy is a neuromuscular Disease in which the Muscle fibers do not function for any one of many reasons resulting in Muscular weakness Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc ^[73] Diseases caused by mutation in the mtDNA include Kearns-Sayre syndrome, MELAS syndrome and Leber's hereditary optic neuropathy. Kearns-Sayre syndrome (abbreviated KSS) or Ragged Red Fiber Myopathy or Oculocraniosomatic Syndrome is a disease caused by a 5000 base deletion in the Mitochondrial Myopathy, Encephalopathy, Lactic acidosis, stroke-like episodes, abbreviated to MELAS is one of the family of Mitochondrial Leber’s hereditary optic neuropathy (LHON or Leber optic atrophy is a mitochondrially inherited (mother to all offspring degeneration of Retinal ^[74] In the vast majority of cases, these diseases are transmitted by a female to her children, as the zygote derives its mitochondria and hence its mtDNA from the ovum. For other meanings see Zygote (disambiguation. A zygote (from Greek ζυγωτός zugōtos "joined" or "yoked" Diseases such as Kearns-Sayre syndrome, Pearson's syndrome, and progressive external ophthalmoplegia are thought to be due to large-scale mtDNA rearrangements, whereas other diseases such as MELAS syndrome, Leber's hereditary optic neuropathy, myoclonic epilepsy with ragged red fibers (MERRF), and others are due to point mutations in mtDNA. Kearns-Sayre syndrome (abbreviated KSS) or Ragged Red Fiber Myopathy or Oculocraniosomatic Syndrome is a disease caused by a 5000 base deletion in the Progressive external ophthalmoplegia is a disorder of the Mitochondria. Mitochondrial Myopathy, Encephalopathy, Lactic acidosis, stroke-like episodes, abbreviated to MELAS is one of the family of Mitochondrial Leber’s hereditary optic neuropathy (LHON or Leber optic atrophy is a mitochondrially inherited (mother to all offspring degeneration of Retinal A point mutation, or single base substitution, is a type of Mutation that causes the replacement of a single base nucleotide with another nucleotide of the genetic ^[73]

In other diseases, defects in nuclear genes lead to dysfunction of mitochondrial proteins. This is the case in Friedreich's ataxia, hereditary spastic paraplegia, and Wilson's disease. Friedreich's ataxia is an Inherited disease that causes progressive damage to the Nervous system resulting in symptoms ranging from Gait disturbance Hereditary Spastic Paraplegia (HSP also called Familial Spastic Paraplegias or Strumpell-Lorrain disease, is not a single disease but is a heterogeneous group of Wilson's disease or hepatolenticular degeneration is an Autosomal recessive Genetic disorder in which Copper accumulates in tissues ^[75] These diseases are inherited in a dominance relationship, as applies to most other genetic diseases. A variety of disorders can be caused by nuclear mutations of oxidative phosphorylation enzymes, such as coenzyme Q10 deficiency and Barth syndrome. Coenzyme Q10 (also known as ubiquinone ubidecarenone coenzyme Q and abbreviated at times to CoQ10 CoQ Q10 or Q is a Benzoquinone, where Q Barth syndrome ( BTHS) also known as 3-Methylglutaconic aciduria type II and Cardiomyopathy-neutropenia syndrome is a rare Genetic disorder classified ^[73] Environmental influences may also interact with hereditary predispositions and cause mitochondrial disease. For example, there may be a link between pesticide exposure and the later onset of Parkinson's disease. A pesticide is a substance or mixture of substances used to kill a pest. Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the Central nervous system that often impairs the sufferer's ^[76][77]

Other diseases not directly linked to mitochondrial enzymes may feature dysfunction of mitochondria. These include schizophrenia, bipolar disorder, dementia, Alzheimer's disease, Parkinson's disease, epilepsy, stroke, cardiovascular disease, retinitis pigmentosa, and diabetes mellitus. Schizophrenia ( from the Greek roots schizein (σχίζειν "to split" and phrēn Dementia (from Latin de- "apart away" + Mens ( genitive mentis) "mind" is the progressive decline Alzheimer's disease ( AD) also called Alzheimer disease or simply Alzheimer's, is the most common form of Dementia. Epilepsy is a common chronic Neurological disorder that is characterized by recurrent unprovoked seizures. A stroke is the rapidly developing loss of brain functions due to a disturbance in the blood vessels supplying blood to the brain Cardiovascular disease or cardiovascular diseases refers to the class of diseases that involve the Heart or Blood vessels ( arteries and Retinitis pigmentosa ( RP) is a group of genetic Eye conditions Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc ^[78][79] The common thread linking these seemingly-unrelated conditions is cellular damage causing oxidative stress and the accumulation of reactive oxygen species. Oxidative stress is caused by an imbalance between the production of reactive oxygen and a biological system's ability to readily detoxify the reactive intermediates or easily Reactive oxygen species (ROS are ions or very small molecules that include Oxygen Ions free radicals, and Peroxides both inorganic and These oxidants then damage the mitochondrial DNA, resulting in mitochondrial dysfunction and cell death. ^[79]

Possible relationships to aging

Given the role of mitochondria as the cell's powerhouse, there may be some leakage of the high-energy electrons in the respiratory chain to form reactive oxygen species. The electron is a fundamental Subatomic particle that was identified and assigned the negative charge in 1897 by J Reactive oxygen species (ROS are ions or very small molecules that include Oxygen Ions free radicals, and Peroxides both inorganic and This can result in significant oxidative stress in the mitochondria with high mutation rates of mitochondrial DNA. Oxidative stress is caused by an imbalance between the production of reactive oxygen and a biological system's ability to readily detoxify the reactive intermediates or easily ^[80] A vicious cycle is thought to occur, as oxidative stress leads to mitochondrial DNA mutations, which can lead to enzymatic abnormalities and further oxidative stress. A number of changes occur to mitochondria during the aging process. ^[81] Tissues from elderly patients show a decrease in enzymatic activity of the proteins of the respiratory chain. ^[82] Large deletions in the mitochondrial genome can lead to high levels of oxidative stress and neuronal death in Parkinson's disease. Oxidative stress is caused by an imbalance between the production of reactive oxygen and a biological system's ability to readily detoxify the reactive intermediates or easily Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the Central nervous system that often impairs the sufferer's ^[83] Hypothesized links between aging and oxidative stress are not new and were proposed over 50 years ago;^[84] however, there is much debate over whether mitochondrial changes are causes of aging or merely characteristics of aging. One notable study in mice demonstrated no increase in reactive oxygen species despite increasing mitochondrial DNA mutations, suggesting that the aging process is not due to oxidative stress. ^[85] As a result, the exact relationships between mitochondria, oxidative stress, and aging have not yet been settled

References

See also

• Anti-mitochondrial antibodies
• Bioenergetics
• Human mitochondrial genetics
• Mitochondrial permeability transition pore
• Submitochondrial particle

External links

• Mitochondria Atlas at University of Mainz
• Mitochondria Research Portal at mitochondrial. Anti-mitochondrial antibodies (AMA are Antibodies ( Immunoglobulins) formed against Mitochondria, primarily mitochondria in cells of the Bioenergetics is the subject of a field of Biochemistry that concerns Energy flow through living systems Mitochondrial genetics is the study of the Genetics of the DNA contained in Mitochondria. Mitochondrial permeability transition, or MPT, is an increase in the permeability of the Mitochondrial membranes to Molecules of less than 1500 Daltons A submitochondrial particle is a compartmentalized membranous product of exposing Mitochondria to ultrasound The Johannes Gutenberg University of Mainz (Johannes Gutenberg-Universität Mainz is a University in Mainz, Rhineland Palatinate, Germany, named net
• Mitochondria: Architecture dictates function at cytochemistry. net
• Mitochondria links at University of Alabama
• Mitochondrion Reconstructed by Electron Tomography at San Diego State University
• Video Clip of Rat-liver Mitochondrion from Cryo-electron Tomography at wadsworth. History Established on March 13 1897 San Diego State University first began as the San Diego Normal School intended to educate local future female elementary school teachers org
• 3D structures of proteins from inner mitochondrial membrane at University of Michigan
• 3D structures of proteins associated with outer mitochondrial membrane at University of Michigan

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