View source for Coenzyme Q - cytochrome c reductase

[[Image:Complex III.png|thumb|250px|schematic illustration of complex III reactions]]
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==Overview==
The '''coenzyme Q : cytochrome ''c'' — oxidoreductase''', sometimes called the '''cytochrome ''bc''<sub>1</sub> complex''', and at other times '''complex III''', is the third complex in the [[electron transport chain]] ({{EC number|1.10.2.2}}), playing a critical role in biochemical generation of ATP ([[oxidative phosphorylation]]). Complex III is a multisubunit transmembrane [[lipoprotein]] encoded by both the mitochondrial ([[cytochrome b]]) and the nuclear genomes (all other subunits). Complex III is present in the mitochondria of all animals and all aerobic eukaryotes and the inner membranes of most eubacteria. Mutations in Complex III cause exercise intolerance as well as multisystem disorders. 

==Reaction==
It catalyzes the reduction of [[Cytochrome c|cytochrome ''c'']] by 
oxidation of [[coenzyme Q]] (CoQ) and the concomitant pumping of 4 [[protons]] from the mitochondrial matrix to the intermembrane space:

: QH<sub>2</sub> + 2 cytochrome ''c'' (Fe<sup>III</sup>)  + 2 H<sup>+</sup><sub>in</sub> → Q + 2 cytochrome ''c'' (Fe<sup>II</sup>) + 4 H<sup>+</sup><sub>out</sub>

In the process called [[Q cycle]],<ref>Kramer, D. M.; Roberts, A. G.; Muller, F.; Cape, J.; Bowman, M. K. Q-cycle bypass reactions at the Qo site of the cytochrome bc1 (and related) complexes. Methods Enzymol. 382:21-45; 2004. PMID 15047094</ref><ref>Crofts, A.R. (2004). The cytochrome bc1 complex: function in the context of structure. Annu Rev Physiol. 66, 689-733. PMID 14977419</ref> two protons are consumed from the matrix (M), four protons are released into the inter membrane space (IM) and two electrons are passed to cytochrome ''c''. 

== Structure ==
Compared to the other major proton pumping subunits of the [[Electron transfer chain|electron transport chain]], the number of subunits found can be small, as small as three polypeptide chains. This number does increase, and eleven subunits are found in higher animals <ref>Iwata S., Lee J.W., Okada K., Lee J.K., Iwata M., Rasmussen B., Link T.A., Ramaswamy S., Jap B.K. (1998) Complete structure of the 11-subunit bovine mitochondrial cytochrome bc1 complex. Science 281: 64-71</ref>. Three subunits have [[prosthetic group]]s. The [[Cytochrome b|cytochrome ''b'' subunit]] has two ''b''-type [[heme]]s (''b''<sub>L</sub> and ''b''<sub>H</sub>), the cytochrome ''c'' sununit has one ''c''-type heme ([[Cytochrome C1|''c''<sub>1</sub>]]), and the Rieske Iron Sulfur Protein subunit (ISP) has a two iron, two sulfur [[iron-sulfur cluster]] (2Fe•2S).

Structures of complex III: {{PDB|1KYO}}, {{PDB|1L0L}}

== Inhibitors of complex III ==
There are three distinct groups of Complex III inhibitors. 
* [[antimycin|Antimycin A]] binds to the Q<sub>i</sub> site and inhibits the transfer of electrons in Complex III from heme ''b''<sub>H</sub> to oxidized Q (Qi site inhibitor). 
* [[Myxothiazol]] and [[stigmatellin]] binds to the Q<sub>o</sub> site and inhibits the transfer of electrons from reduced QH<sub>2</sub> to the Rieske Iron sulfur protein. Myxothiazol and stigmatellin bind to distinct pockets within the Q<sub>o</sub> site. 
** Myxothiazol binds very close to cytochrome bL (hence termed a "proximal" inhibitor).
** Stigmatellin binds near the Rieske Iron sulfur protein, with which it strongly interacts. 

Some have been commercialized as fungicides (the [[strobilurin]] derivates) and as anti-malaria agents ([[atovaquone]]).

== Oxygen free radicals ==
A small fraction of electrons leave the electron transport chain before reaching [[complex IV]]. Premature electron leakage to [[oxygen]] results in the formation of [[superoxide]]. The relevance of this otherwise minor side reaction is that [[superoxide]] and other [[reactive oxygen species]] are highly toxic and are thought to play a role in several pathologies, including aging (the [[free radical theory of aging]]). Electron leakage occurs mainly at the Q<sub>o</sub> site and is stimulated by [[antimycin A]]. [[Antimycin A]] locks the ''b'' hemes in the reduced state by preventing their re-oxidation at the Q<sub>i</sub> site, which in turn causes the steady state concentrations of the Q<sub>o</sub> semiquinone to rise, the latter species reacting with [[oxygen]] to form [[superoxide]]. The effect of high membrane potential is thought to have a similar effect <ref>Skulachev, V. P. (1996) Role of uncoupled and non-coupled oxidations in maintenance of safely low levels of oxygen and its one-electron reductants. Q. Rev. Biophys. 29, 169-202
</ref>. [[Superoxide]] produced at the Qo site can be released both into the mitochondrial matrix <ref>Muller, F. (2000) The Nature and Mechanism of Superoxide production by the Electron Transport Chain: Its relevance to aging. J. Amer. Aging Assoc. 23, 227-253</ref><ref>Muller, F. L., Liu, Y. and Van Remmen, H. (2004) Complex III Releases superoxide to both sides of the inner mitochondrial membrane. J. Biol. Chem. 279, 49064-49073
</ref> and intermembrane space (from where it can reach the cytosol <ref>Han, D., Williams, E. and Cadenas, E. (2001) Mitochondrial respiratory chain-dependent generation of superoxide anion and its release into the intermembrane space. Biochem. J. 353, 411-416.
</ref><ref>Muller, F. (2000) The Nature and Mechanism of Superoxide production by the Electron Transport Chain: Its relevance to aging. J. Amer. Aging Assoc. 23, 227-253
</ref>). This could be explained by the fact that Complex III might produce [[superoxide]] as membrane permeable [[HO2]] rather than as membrane impermeable O2- <ref>Muller, F. L., Liu, Y. and Van Remmen, H. (2004) Complex III Releases superoxide to both sides of the inner mitochondrial membrane. J. Biol. Chem. 279, 49064-49073
</ref>.

== References ==
{{reflist}}

== See also ==
*[[Cellular respiration]]
*[[Photosynthetic reaction centre]]

==Additional images==
<gallery>
 Image:ETC.PNG|ETC
 Image:Etc2.png|ETC
</gallery>

== External links ==
* [http://sb20.lbl.gov/cytbc1 cytochrome ''bc''<sub>1</sub> complex site (Edward A. Berry)] at lbl.gov
* [http://www.life.uiuc.edu/crofts/bc-complex_site cytochrome ''bc''<sub>1</sub> complex site (Antony R. Crofts)] at uiuc.edu
* [http://metallo.scripps.edu/PROMISE/CYTBC1.html PROMISE Database: cytochrome ''bc''<sub>1</sub> complex] at scripps.edu
* [http://www.ufp.pt/~pedros/anim/2frame-iiien.htm Interactive Molecular Model of Complex III] (Requires [http://www.mdl.com/products/framework/chime/ MDL Chime])
* {{UMichOPM|families|superfamily|3}} - Calculated positions of bc1 and related complexes in membranes
* {{MeshName|Coenzyme+Q-Cytochrome-c+Reductase}}

{{Diphenol family oxidoreductases}}
{{Electron transport chain}}
{{Proton pumps}}
{{Mitochondrial DNA}}
{{SIB}}

[[Category:Cellular respiration]]
[[Category:EC 1.10.2]]
[[Category:Iron-sulfur proteins]]
[[Category:Integral membrane proteins]]

[[de:Cytochrom c Reduktase]]
[[fr:Coenzyme Q - cytochrome c-réductase]]
[[it:Ubiquinolo-citocromo c reduttasi]]

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