- Cytochrome c
Cytochrome c, somatic
Three-dimensional structure of cytochrome c (green) with a heme molecule coordinating a central Iron atom (orange).
Available structures PDB , Identifiers Symbols External IDs GeneCards: Gene Ontology Molecular function •
Cellular component •
Biological process •
Sources: Amigo / QuickGO RNA expression pattern Orthologs Species Human Mouse Entrez Ensembl n/a UniProt n/a RefSeq (mRNA) RefSeq (protein) Location (UCSC) n/a PubMed search
The Cytochrome complex, or cyt c is a small heme protein found loosely associated with the inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins. Cytochrome c is a highly soluble protein, unlike other cytochromes, with a solubility of about 100 g/L and is an essential component of the electron transport chain, where it carries one electron. It is capable of undergoing oxidation and reduction, but does not bind oxygen. It transfers electrons between Complexes III (Coenzyme Q - Cyt C reductase) and IV (Cyt C oxidase). In humans, cytochrome c is encoded by the CYCS gene.
Cytochrome c is a component of the electron transport chain in mitochondria. The heme group of cytochrome c accepts electrons from the b-c1 complex and transfers electrons to the cytochrome oxidase complex. Cytochrome c is also involved in initiation of apoptosis. Upon release of cytochrome c to the cytoplasm, the protein binds apoptotic protease activating factor.
Cytochrome c can catalyze several reactions such as hydroxylation and aromatic oxidation, and shows peroxidase activity by oxidation of various electron donors such as 2,2-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS), 2-keto-4-thiomethyl butyric acid and 4-aminoantipyrine.
Cytochrome c is a highly conserved protein across the spectrum of species, found in plants, animals, and many unicellular organisms. This, along with its small size (molecular weight about 12,000 daltons), makes it useful in studies of cladistics. Its primary structure consists of a chain of about 100 amino acids. Many higher order organisms possess a chain of 104 amino acids.
The cytochrome c molecule has been studied for the glimpse it gives into evolutionary biology. Both chickens and turkeys have identical sequence homology (amino acid for amino acid), whereas ducks possess molecules differing by one amino acid. Similarly, both humans and chimpanzees have the identical molecule, while rhesus monkeys share all but one of the amino acids: the 66th amino acid is isoleucine in the former and threonine in the latter. Pigs, cows and sheep also share identical cytochrome c molecules.
In 1991 R. P. Ambler recognized four classes of cytochrome c:
- Class I includes the lowspin soluble cytochrome c of mitochondria and bacteria. It has the heme-attachment site towards the N terminus of histidine and the sixth ligand provided by a methionine residue towards the C terminus.
- Class II includes the highspin cytochrome c'. It has the heme-attachment site closed to the N terminus of histidine.
- Class III comprises the low redox potential multiple heme cytochromes. The heme c groups are structurally and functionally nonequivalent and present different redox potentials in the range 0 to -400 mV.
- Class IV was originally created to hold the complex proteins that have other prosthetic groups as well as heme c.
Cytochrome c is suspected to be the functional complex in so called LLLT: Low-level laser therapy. In LLLT, red light and some near infra-red wavelengths penetrate tissue in order to increase cellular regeneration. Light of this wavelength appears capable of increasing activity of cytochrome c, thus increasing metabolic activity and freeing up more energy for the cells to repair the tissue.
Role in apoptosis
Cytochrome c is released by the mitochondria in response to pro-apoptotic stimuli. The sustained elevation in calcium levels precedes cyt c release from the mitochondria. The release of small amounts of cyt c leads to an interaction with the IP3 receptor (IP3R) on the endoplasmic reticulum (ER), causing ER calcium release. The overall increase in calcium triggers a massive release of cyt c, which then acts in the positive feedback loop to maintain ER calcium release through the IP3Rs. This explains how the ER calcium release can reach cytotoxic levels. This release of cytochrome c in turn activates caspase 9, a cysteine protease. Caspase 9 can then go on to activate caspase 3 and caspase 7, which are responsible for destroying the cell from within.
Cytochrome c binds to cardiolipin in the inner mitochondrial membrane, thus anchoring its presence and keeping it from releasing out of the mitochondria and initiating apoptosis. While the initial attraction between cardiolipin and cytochrome c is electrostatic due to the extreme positive charge on cytochrome c, the final interaction is hydrophobic, where a hydrophobic tail from cardiolipin inserts itself into the hydrophobic portion of cytochrome c.
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- The Cytochrome c Protein
- Apoptosis & Caspase 3 - PMAP The Proteolysis Map-animation
- UMich Orientation of Proteins in Membranes families/superfamily-78 - Calculated orientations of cytochromes c in the lipid bilayer
- MeSH Cytochrome+c
PDB gallery Metabolism: Citric acid cycle enzymes Cycle Anapleroticto acetyl-CoAto succinyl-CoAto oxaloacetate Mitochondrial
electron transport chain/
Apoptosis signaling pathway Fas pathIntracellular TNF pathIntracellular OtherIntracellular
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