The coenzyme Q : cytochrome ''c'' – oxidoreductase, sometimes called the cytochrome ''bc''
1 complex, and at other times complex III, is the third complex in the
electron transport chain
An electron transport chain (ETC) is a series of protein complexes and other molecules which transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples th ...
(), playing a critical role in biochemical generation of ATP (
oxidative phosphorylation
Oxidative phosphorylation(UK , US : or electron transport-linked phosphorylation or terminal oxidation, is the metabolic pathway in which Cell (biology), cells use enzymes to Redox, oxidize nutrients, thereby releasing chemical energy in order ...
). Complex III is a multisubunit transmembrane protein encoded by both the mitochondrial (
cytochrome b
Cytochrome b is a protein found in the membranes of aerobic cells. In eukaryotic mitochondria (inner membrane) and in aerobic prokaryotes, cytochrome b is a component of respiratory chain complex III () — also known as the bc1 complex or ubiq ...
) and the nuclear genomes (all other subunits). Complex III is present in the
mitochondria
A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...
of all animals and all aerobic eukaryotes and the inner membranes of most
bacteria
Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...
. Mutations in Complex III cause
exercise intolerance
Exercise intolerance is a condition of inability or decreased ability to perform physical exercise at the normally expected level or duration for people of that age, size, sex, and muscle mass. It also includes experiences of unusually severe pos ...
as well as multisystem disorders. The bc1
complex
Complex commonly refers to:
* Complexity, the behaviour of a system whose components interact in multiple ways so possible interactions are difficult to describe
** Complex system, a system composed of many components which may interact with each ...
contains 11 subunits, 3 respiratory
subunits (cytochrome B,
cytochrome
Cytochromes are redox-active proteins containing a heme, with a central iron (Fe) atom at its core, as a cofactor. They are involved in the electron transport chain and redox catalysis. They are classified according to the type of heme and its ...
C1, Rieske protein), 2 core
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
s and 6 low-molecular weight
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
s.
Ubiquinol—cytochrome-c reductase catalyzes the chemical reaction
:QH
2 + 2 ferricytochrome c
Q + 2 ferrocytochrome c + 2 H
+
Thus, the two
substrates of this enzyme are quinol (QH
2) and ferri- (Fe
3+)
cytochrome c, whereas its 3
products
Product may refer to:
Business
* Product (business), an item that can be offered to a market to satisfy the desire or need of a customer.
* Product (project management), a deliverable or set of deliverables that contribute to a business solution
...
are
quinone
The quinones are a class of organic compounds that are formally "derived from aromatic compounds benzene.html" ;"title="uch as benzene">uch as benzene or naphthalene] by conversion of an even number of –CH= groups into –C(=O)– groups with ...
(Q), ferro- (Fe
2+) cytochrome c, and
+">hydrogen ion, H+.
This enzyme belongs to the family of
oxidoreductase
In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule, the reductant, also called the electron donor, to another, the oxidant, also called the electron acceptor. This group of enzymes usually ut ...
s, specifically those acting on diphenols and related substances as donor with a cytochrome as acceptor. This enzyme participates in
oxidative phosphorylation
Oxidative phosphorylation(UK , US : or electron transport-linked phosphorylation or terminal oxidation, is the metabolic pathway in which Cell (biology), cells use enzymes to Redox, oxidize nutrients, thereby releasing chemical energy in order ...
. It has four
cofactors:
cytochrome c1,
cytochrome b-562, cytochrome b-566, and a 2-Iron
ferredoxin
Ferredoxins (from Latin ''ferrum'': iron + redox, often abbreviated "fd") are iron–sulfur proteins that mediate electron transfer in a range of metabolic reactions. The term "ferredoxin" was coined by D.C. Wharton of the DuPont Co. and applied t ...
of the
Rieske type.
Nomenclature
The
systematic name
A systematic name is a name given in a systematic way to one unique group, organism, object or chemical substance, out of a specific population or collection. Systematic names are usually part of a nomenclature.
A semisystematic name or semitrivi ...
of this enzyme class is ubiquinol:ferricytochrome-c oxidoreductase. Other names in common use include:
Structure

Compared to the other major proton-pumping subunits of the
electron transport chain
An electron transport chain (ETC) is a series of protein complexes and other molecules which transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples th ...
, 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.
Three subunits have
prosthetic group
A prosthetic group is the non-amino acid component that is part of the structure of the heteroproteins or conjugated proteins, being tightly linked to the apoprotein.
Not to be confused with the cosubstrate that binds to the enzyme apoenzyme (e ...
s. The
cytochrome ''b'' subunit has two ''b''-type
heme
Heme (American English), or haem (Commonwealth English, both pronounced /Help:IPA/English, hi:m/ ), is a ring-shaped iron-containing molecule that commonly serves as a Ligand (biochemistry), ligand of various proteins, more notably as a Prostheti ...
s (''b''
L and ''b''
H), the cytochrome ''c'' subunit has one ''c''-type heme (
''c''1), and the Rieske Iron Sulfur Protein subunit (ISP) has a two iron, two sulfur
iron-sulfur cluster (2Fe•2S).
Structures of complex III: ,
Composition of complex
In vertebrates the bc
1 complex, or Complex III, contains 11 subunits: 3 respiratory subunits, 2 core proteins and 6 low-molecular weight proteins.
Proteobacterial complexes may contain as few as three subunits.
Table of subunit composition of complex III
*
a In vertebrates, a cleavage product of 8 kDa from the N-terminus of the Rieske protein (
Signal peptide
A signal peptide (sometimes referred to as signal sequence, targeting signal, localization signal, localization sequence, transit peptide, leader sequence or leader peptide) is a short peptide (usually 16–30 amino acids long) present at the ...
) is retained in the complex as subunit 9. Thus subunits 10 and 11 correspond to fungal QCR9p and QCR10p.
Reaction

It catalyzes the reduction of
cytochrome ''c'' by
oxidation of
coenzyme Q (CoQ) and the concomitant pumping of 4
protons
A proton is a stable subatomic particle, symbol , H+, or 1H+ with a positive electric charge of +1 ''e'' ( elementary charge). Its mass is slightly less than the mass of a neutron and approximately times the mass of an electron (the pro ...
from the mitochondrial matrix to the intermembrane space:
: QH
2 + 2 cytochrome ''c'' (Fe
III) + 2 H → Q + 2 cytochrome ''c'' (Fe
II) + 4 H
In the process called
Q cycle
The Q cycle (named for ''quinol'') describes a series of sequential oxidation and reduction of the lipophilic electron carrier Coenzyme Q (CoQ) between the ubiquinol and ubiquinone forms. These reactions can result in the net movement of proton ...
,
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''.
Reaction mechanism

The reaction mechanism for complex III (cytochrome bc1, coenzyme Q: cytochrome C oxidoreductase) is known as the ubiquinone ("Q") cycle. In this cycle four protons get released into the positive "P" side (inter membrane space), but only two protons get taken up from the negative "N" side (matrix). As a result, a
proton gradient
An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts:
* The chemical gradient, or difference in solute concentration across a membrane.
...
is formed across the membrane. In the overall reaction, two
ubiquinol
A ubiquinol is an electron-rich (reduced) form of coenzyme Q (ubiquinone). The term most often refers to ubiquinol-10, with a 10-unit tail most commonly found in humans.
The natural ubiquinol form of coenzyme Q is 2,3-dimethoxy-5-methyl-6-poly p ...
s are oxidized to
ubiquinone
Coenzyme Q10 (CoQ10 ), also known as ubiquinone, is a naturally occurring Cofactor (biochemistry), biochemical cofactor (coenzyme) and an antioxidant produced by the human body. It can also be obtained from dietary sources, such as meat, fish, ...
s and one
ubiquinone
Coenzyme Q10 (CoQ10 ), also known as ubiquinone, is a naturally occurring Cofactor (biochemistry), biochemical cofactor (coenzyme) and an antioxidant produced by the human body. It can also be obtained from dietary sources, such as meat, fish, ...
is reduced to
ubiquinol
A ubiquinol is an electron-rich (reduced) form of coenzyme Q (ubiquinone). The term most often refers to ubiquinol-10, with a 10-unit tail most commonly found in humans.
The natural ubiquinol form of coenzyme Q is 2,3-dimethoxy-5-methyl-6-poly p ...
. In the complete mechanism, two electrons are transferred from ubiquinol to ubiquinone, via two cytochrome c intermediates.
Overall:
* 2 x QH
2 oxidised to Q
* 1 x Q reduced to QH
2
* 2 x Cyt c reduced
* 4 x H
+ released into intermembrane space
* 2 x H
+ picked up from matrix
The reaction proceeds according to the following steps:
Round 1:
# Cytochrome b binds a ubiquinol and a ubiquinone.
# The 2Fe/2S center and B
L heme each pull an electron off the bound ubiquinol, releasing two protons into the intermembrane space.
# One electron is transferred to cytochrome c
1 from the 2Fe/2S centre, whilst another is transferred from the B
L heme to the B
H Heme.
# Cytochrome c
1 transfers its electron to
cytochrome c (not to be confused with cytochrome c1), and the B
H Heme transfers its electron to a nearby ubiquinone, resulting in the formation of a ubisemiquinone.
# Cytochrome c diffuses. The first ubiquinol (now oxidised to ubiquinone) is released, whilst the semiquinone remains bound.
Round 2:
# A second ubiquinol is bound by cytochrome b.
# The 2Fe/2S center and B
L heme each pull an electron off the bound ubiquinol, releasing two protons into the intermembrane space.
# One electron is transferred to cytochrome c
1 from the 2Fe/2S centre, whilst another is transferred from the B
L heme to the B
H Heme.
# Cytochrome c
1 then transfers its electron to
cytochrome c, whilst the nearby semiquinone produced from round 1 picks up a second electron from the B
H heme, along with two protons from the matrix.
# The second ubiquinol (now oxidised to ubiquinone), along with the newly formed ubiquinol are released.
Inhibitors of complex III
There are three distinct groups of Complex III inhibitors.
*
Antimycin A binds to the Q
i site and inhibits the transfer of electrons in Complex III from heme ''b''
H to oxidized Q (Qi site inhibitor).
*
Myxothiazol and
stigmatellin binds to the Q
o site and inhibits the transfer of electrons from reduced QH
2 to the Rieske Iron sulfur protein. Myxothiazol and stigmatellin bind to distinct but overlapping pockets within the Q
o site.
** Myxothiazol binds nearer to cytochrome bL (hence termed a "
proximal
Standard anatomical terms of location are used to describe unambiguously the anatomy of humans and other animals. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position prov ...
" inhibitor).
** Stigmatellin binds farther from heme bL and nearer the Rieske Iron sulfur protein, with which it strongly interacts.
Some have been commercialized as fungicides (the
strobilurin derivatives, best known of which is
azoxystrobin;
QoI inhibitors) and as anti-malaria agents (
atovaquone). Some Q
o site inhibitors have been commercialized as insecticides (
IRAC group 20).
Also
propylhexedrine inhibits cytochrome c reductase.
Oxygen free radicals
A small fraction of electrons leave the electron transport chain before reaching
complex IV. Premature electron leakage to
oxygen
Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...
results in the formation of
superoxide
In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formula . The systematic name of the anion is dioxide(1−). The reactive oxygen ion superoxide is particularly important as the product of t ...
. The relevance of this otherwise minor side reaction is that
superoxide
In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formula . The systematic name of the anion is dioxide(1−). The reactive oxygen ion superoxide is particularly important as the product of t ...
and other
reactive oxygen species
In chemistry and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl ...
are highly toxic and are thought to play a role in several pathologies, as well as aging (the
free radical theory of aging
Free may refer to:
Concept
* Freedom, the ability to act or change without constraint or restriction
* Emancipate, attaining civil and political rights or equality
* Free (''gratis''), free of charge
* Gratis versus libre, the difference bet ...
).
Electron leakage occurs mainly at the Q
o 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
i site, which, in turn, causes the steady-state concentrations of the Q
o semiquinone to rise, the latter species reacting with
oxygen
Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...
to form
superoxide
In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formula . The systematic name of the anion is dioxide(1−). The reactive oxygen ion superoxide is particularly important as the product of t ...
. The effect of high membrane potential is thought to have a similar effect.
Superoxide
In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formula . The systematic name of the anion is dioxide(1−). The reactive oxygen ion superoxide is particularly important as the product of t ...
produced at the Qo site can be released both into the mitochondrial matrix
and into the intermembrane space, where it can then reach the cytosol.
This could be explained by the fact that Complex III might produce
superoxide
In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formula . The systematic name of the anion is dioxide(1−). The reactive oxygen ion superoxide is particularly important as the product of t ...
as membrane permeable
HOO• rather than as membrane impermeable
O.
Human gene names
*
MT-CYB
Cytochrome b is a protein that in humans is encoded by the ''MT-CYB'' gene. Its gene product is a subunit of the respiratory chain protein ubiquinol–cytochrome ''c'' reductase (UQCR, complex III or cytochrome ''bc''1 complex), which consists ...
:
mtDNA
Mitochondrial DNA (mtDNA and mDNA) is the DNA located in the mitochondria organelles in a eukaryotic cell that converts chemical energy from food into adenosine triphosphate (ATP). Mitochondrial DNA is a small portion of the DNA contained in ...
encoded cytochrome b; mutations associated with exercise intolerance
*
CYC1: cytochrome c1
*
CYCS: cytochrome c
*
UQCRFS1: Rieske iron sulfur protein
*
UQCRB: Ubiquinone binding protein, mutation linked with mitochondrial complex III deficiency nuclear type 3
*
UQCRH: hinge protein
*
UQCRC2: Core 2, mutations linked to mitochondrial complex III deficiency, nuclear type 5
*
UQCRC1: Core 1
*
UQCR: 6.4KD subunit
*
UQCR10: 7.2KD subunit
*
TTC19: Newly identified subunit, mutations linked to complex III deficiency nuclear type 2. Helps remove the N-terminal fragment of UQCRFS1, which would otherwise interfere with complex III function.
Mutations in complex III genes in human disease
Mutations in complex III-related genes typically manifest as exercise intolerance.
Other mutations have been reported to cause
septo-optic dysplasia and multisystem disorders.
However, mutations in
BCS1L, a gene responsible for proper maturation of complex III, can result in
Björnstad syndrome and the
GRACILE syndrome, which in neonates are lethal conditions that have multisystem and neurologic manifestations typifying severe mitochondrial disorders. The pathogenicity of several mutations has been verified in model systems such as yeast.
The extent to which these various pathologies are due to bioenergetic deficits or overproduction of
superoxide
In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formula . The systematic name of the anion is dioxide(1−). The reactive oxygen ion superoxide is particularly important as the product of t ...
is presently unknown.
See also
*
Cellular respiration
Cellular respiration is the process of oxidizing biological fuels using an inorganic electron acceptor, such as oxygen, to drive production of adenosine triphosphate (ATP), which stores chemical energy in a biologically accessible form. Cell ...
*
Photosynthetic reaction centre
A photosynthetic reaction center is a complex of several proteins, biological pigments, and other co-factors that together execute the primary energy conversion reactions of photosynthesis. Molecular excitations, either originating directly from ...
Additional images
File:Mitochondrial electron transport chain (annotated diagram).svg, ETC
References
Further reading
*
*
*
External links
* at lbl.gov
cytochrome ''bc''1 complex site (Antony R. Crofts) at uiuc.edu
* at scripps.edu
* (Require
MDL Chime
* - Calculated positions of bc1 and related complexes in membranes
*
#124000 MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 1; MC3DN1on
OMIM
Online Mendelian Inheritance in Man (OMIM) is a continuously updated catalog of human genes and genetic disorders and traits, with a particular focus on the gene-phenotype relationship. , approximately 9,000 of the over 25,000 entries in OMIM ...
; lists all other types of complex III deficiency
{{DEFAULTSORT:Coenzyme Q - cytochrome c reductase
EC 7.1.1
Enzymes of known structure
Cellular respiration
Iron–sulfur proteins
Transmembrane proteins