A mitochondrial protein-coding gene whose product is involved in the respiratory chain
Location of the MT-CYB gene in the human mitochondrial genome (coral box).
Cytochrome b is a
protein that in humans is encoded by the MT-CYB gene .
[5] 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 of the products of one mitochondrially encoded gene, MT-CYB (mitochondrial
cytochrome b ), and ten nuclear genes—
UQCRC1 ,
UQCRC2 ,
CYC1 ,
UQCRFS1 (
Rieske protein ),
UQCRB , "11kDa protein",
UQCRH (cyt c1 Hinge protein), Rieske protein presequence, "cyt c1 associated protein", and
Rieske-associated protein .
Structure
The MT-CYB gene is located on the p arm of
mitochondrial DNA in position 12 and spans 1,140 base pairs.
[5] The gene produces a 42.7 kDa protein named
cytochrome b composed of 380
amino acids .
[6]
[7]
Cytochrome b is an integral membrane protein with hydrophobic properties. The catalytic core of the enzyme is composed of eight transmembrane helices, the
iron-sulfur protein , and
cytochrome c1 .
[8]
Cytochrome b is a fundamental component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex) that is part of the
mitochondrial respiratory chain . The b-c1 complex mediates electron transfer from
ubiquinol to cytochrome c.
[9] The structure of the complex is a symmetric homodimer. It is composed of eleven structural subunits, including one
mitochondrial genome encoded cytochrome b and ten other nucleus encoded subunits. These subunits include three respiratory subunits (MT-CYB,
CYC1 and
UQCRFS1 ), two core proteins (
UQCRC1 and
UQCRC2 ) and six low-molecular weight proteins (
UQCRH /
QCR6 ,
UQCRB /
QCR7 ,
UQCRQ /
QCR8 ,
UQCR10 /
QCR9 ,
UQCR11 /
QCR10 and a cleavage product of
UQCRFS1 ). The total
molecular mass of the complex is about 450 kDa.
[10]
[9]
Function
The mitochondrial
cytochrome b is fundamental for the assembly and function of Complex III of the
mitochondrial respiratory chain .
[11] Complex III is responsible for the
catalysis of electron transfer from
coenzyme Q to
cytochrome c in the
mitochondrial respiratory chain by translocating protons concomitantly across the
inner membrane of the mitochondria .
[12]
[9] The transfer of electrons then contributes to the generation of a
proton gradient across the
mitochondrial membrane that is then used for ATP synthesis.
[9]
Clinical significance
Mutations in MT-CYB can result in mitochondrial deficiencies and associated disorders. It is majorly associated with a complex III deficiency, a deficiency in an enzyme complex which catalyzes electron transfer from
coenzyme Q to
cytochrome c in the
mitochondrial respiratory chain . A complex III deficiency can result in a highly variable phenotype depending on which tissues are affected.
[9] Most frequent clinical manifestations include progressive
exercise intolerance and
cardiomyopathy . Occasional multisystem disorders accompanied by exercise intolerance may arise as well, in forms of
deafness ,
mental retardation ,
retinitis pigmentosa ,
cataract ,
growth retardation , and
epilepsy .
[9] Other phenotypes include mitochondrial
encephalomyopathy ,
mitochondrial myopathy ,
Leber hereditary optic neuropathy ,
muscle weakness ,
myoglobinuria ,
blood acidosis , renal
tubulopathy , and more.
[9]
[10] Complex III deficiency is known to be rare among
mitochondrial diseases and may follow a
maternal or
mendelian mode of inheritance due to its duality of genetic origin.
[8]
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000198727 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000064370 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
a
b
"Entrez Gene: CYTB cytochrome b" .
^ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (Oct 2013).
"Integration of cardiac proteome biology and medicine by a specialized knowledgebase" . Circulation Research . 113 (9): 1043–53.
doi :
10.1161/CIRCRESAHA.113.301151 .
PMC
4076475 .
PMID
23965338 .
^
"cytochrome b" . Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) .
^
a
b Fragaki K, Procaccio V, Bannwarth S, Serre V, O'Hearn S, Potluri P, Augé G, Casagrande F, Caruba C, Lambert JC, Paquis-Flucklinger V (September 2009). "A neonatal polyvisceral failure linked to a de novo homoplasmic mutation in the mitochondrially encoded cytochrome b gene". Mitochondrion . 9 (5): 346–52.
doi :
10.1016/j.mito.2009.06.002 .
PMID
19563916 .
^
a
b
c
d
e
f
g
"UniProtKB - P00156 (CYB_HUMAN)" . The UniProt Consortium.
^
a
b Gil Borlado MC, Moreno Lastres D, Gonzalez Hoyuela M, Moran M, Blazquez A, Pello R, Marin Buera L, Gabaldon T, Garcia Peñas JJ, Martín MA, Arenas J, Ugalde C (September 2010).
"Impact of the mitochondrial genetic background in complex III deficiency" . PLOS ONE . 5 (9): e12801.
Bibcode :
2010PLoSO...512801G .
CiteSeerX
10.1.1.350.7243 .
doi :
10.1371/journal.pone.0012801 .
PMC
2941448 .
PMID
20862300 .
^ Massie R, Wong LJ, Milone M (July 2010). "Exercise intolerance due to cytochrome b mutation". Muscle & Nerve . 42 (1): 136–40.
doi :
10.1002/mus.21649 .
PMID
20544923 .
S2CID
23759055 .
^ Baum H, Rieske JS, Silman HI, Lipton SH (March 1967).
"On the mechanism of electron transfer in complex iii of the electron transfer chain" . Proceedings of the National Academy of Sciences of the United States of America . 57 (3): 798–805.
Bibcode :
1967PNAS...57..798B .
doi :
10.1073/pnas.57.3.798 .
PMC
335578 .
PMID
16591533 .
Further reading
Ingman M, Kaessmann H, Pääbo S, Gyllensten U (Dec 2000). "Mitochondrial genome variation and the origin of modern humans". Nature . 408 (6813): 708–13.
Bibcode :
2000Natur.408..708I .
doi :
10.1038/35047064 .
PMID
11130070 .
S2CID
52850476 .
Maca-Meyer N, González AM, Larruga JM, Flores C, Cabrera VM (2003).
"Major genomic mitochondrial lineages delineate early human expansions" . BMC Genetics . 2 : 13.
doi :
10.1186/1471-2156-2-13 .
PMC
55343 .
PMID
11553319 .
Herrnstadt C, Elson JL, Fahy E, Preston G, Turnbull DM, Anderson C, Ghosh SS, Olefsky JM, Beal MF, Davis RE, Howell N (May 2002).
"Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups" . American Journal of Human Genetics . 70 (5): 1152–71.
doi :
10.1086/339933 .
PMC
447592 .
PMID
11938495 .
Silva WA, Bonatto SL, Holanda AJ, Ribeiro-Dos-Santos AK, Paixão BM, Goldman GH, Abe-Sandes K, Rodriguez-Delfin L, Barbosa M, Paçó-Larson ML, Petzl-Erler ML, Valente V, Santos SE, Zago MA (Jul 2002).
"Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America" . American Journal of Human Genetics . 71 (1): 187–92.
doi :
10.1086/341358 .
PMC
384978 .
PMID
12022039 .
Yamasoba T, Goto Yi, Oka Y, Nishino I, Tsukuda K, Nonaka I (Jun 2002). "Atypical muscle pathology and a survey of cis-mutations in deaf patients harboring a 1555 A-to-G point mutation in the mitochondrial ribosomal RNA gene". Neuromuscular Disorders . 12 (5): 506–12.
doi :
10.1016/S0960-8966(01)00329-7 .
PMID
12031626 .
S2CID
37695849 .
Mishmar D, Ruiz-Pesini E, Golik P, Macaulay V, Clark AG, Hosseini S, Brandon M, Easley K, Chen E, Brown MD, Sukernik RI, Olckers A, Wallace DC (Jan 2003).
"Natural selection shaped regional mtDNA variation in humans" . Proceedings of the National Academy of Sciences of the United States of America . 100 (1): 171–6.
Bibcode :
2003PNAS..100..171M .
doi :
10.1073/pnas.0136972100 .
PMC
140917 .
PMID
12509511 .
Mancuso M, Filosto M, Stevens JC, Patterson M, Shanske S, Krishna S, DiMauro S (May 2003). "Mitochondrial myopathy and complex III deficiency in a patient with a new stop-codon mutation (G339X) in the cytochrome b gene". Journal of the Neurological Sciences . 209 (1–2): 61–3.
doi :
10.1016/S0022-510X(02)00462-8 .
PMID
12686403 .
S2CID
31605529 .
Ingman M, Gyllensten U (Jul 2003).
"Mitochondrial genome variation and evolutionary history of Australian and New Guinean aborigines" . Genome Research . 13 (7): 1600–6.
doi :
10.1101/gr.686603 .
PMC
403733 .
PMID
12840039 .
Kong QP, Yao YG, Sun C, Bandelt HJ, Zhu CL, Zhang YP (Sep 2003).
"Phylogeny of east Asian mitochondrial DNA lineages inferred from complete sequences" . American Journal of Human Genetics . 73 (3): 671–6.
doi :
10.1086/377718 .
PMC
1180693 .
PMID
12870132 .
Kong QP, Yao YG, Liu M, Shen SP, Chen C, Zhu CL, Palanichamy MG, Zhang YP (Oct 2003). "Mitochondrial DNA sequence polymorphisms of five ethnic populations from northern China". Human Genetics . 113 (5): 391–405.
doi :
10.1007/s00439-003-1004-7 .
PMID
12938036 .
S2CID
6370358 .
Maca-Meyer N, González AM, Pestano J, Flores C, Larruga JM, Cabrera VM (Oct 2003).
"Mitochondrial DNA transit between West Asia and North Africa inferred from U6 phylogeography" . BMC Genetics . 4 : 15.
doi :
10.1186/1471-2156-4-15 .
PMC
270091 .
PMID
14563219 .
Haut S, de Villemeur TB, Brivet M, Guiochon-Mantel A, Boutron A, Rustin P, Legrand A, Slama A (Mar 2004).
"The deleterious G15498A mutation in mitochondrial DNA-encoded cytochrome b may remain clinically silent in homoplasmic carriers" . European Journal of Human Genetics . 12 (3): 220–4.
doi :
10.1038/sj.ejhg.5201132 .
PMID
14735157 .
Palanichamy MG, Sun C, Agrawal S, Bandelt HJ, Kong QP, Khan F, Wang CY, Chaudhuri TK, Palla V, Zhang YP (Dec 2004).
"Phylogeny of mitochondrial DNA macrohaplogroup N in India, based on complete sequencing: implications for the peopling of South Asia" . American Journal of Human Genetics . 75 (6): 966–78.
doi :
10.1086/425871 .
PMC
1182158 .
PMID
15467980 .
Starikovskaya EB, Sukernik RI, Derbeneva OA, Volodko NV, Ruiz-Pesini E, Torroni A, Brown MD, Lott MT, Hosseini SH, Huoponen K, Wallace DC (Jan 2005).
"Mitochondrial DNA diversity in indigenous populations of the southern extent of Siberia, and the origins of Native American haplogroups" . Annals of Human Genetics . 69 (Pt 1): 67–89.
doi :
10.1046/j.1529-8817.2003.00127.x .
PMC
3905771 .
PMID
15638829 .
Rajkumar R, Banerjee J, Gunturi HB, Trivedi R, Kashyap VK (2006).
"Phylogeny and antiquity of M macrohaplogroup inferred from complete mt DNA sequence of Indian specific lineages" . BMC Evolutionary Biology . 5 : 26.
doi :
10.1186/1471-2148-5-26 .
PMC
1079809 .
PMID
15804362 .
Thangaraj K, Chaubey G, Kivisild T, Reddy AG, Singh VK, Rasalkar AA, Singh L (May 2005). "Reconstructing the origin of Andaman Islanders". Science . 308 (5724): 996.
doi :
10.1126/science.1109987 .
PMID
15890876 .
S2CID
12011171 .
Blakely EL, Mitchell AL, Fisher N, Meunier B, Nijtmans LG, Schaefer AM, Jackson MJ, Turnbull DM, Taylor RW (Jul 2005).
"A mitochondrial cytochrome b mutation causing severe respiratory chain enzyme deficiency in humans and yeast" . The FEBS Journal . 272 (14): 3583–92.
doi :
10.1111/j.1742-4658.2005.04779.x .
PMID
16008558 .
Kivisild T, Shen P, Wall DP, Do B, Sung R, Davis K, Passarino G, Underhill PA, Scharfe C, Torroni A, Scozzari R, Modiano D, Coppa A, de Knijff P, Feldman M, Cavalli-Sforza LL, Oefner PJ (Jan 2006).
"The role of selection in the evolution of human mitochondrial genomes" . Genetics . 172 (1): 373–87.
doi :
10.1534/genetics.105.043901 .
PMC
1456165 .
PMID
16172508 .
Behar DM, Metspalu E, Kivisild T, Achilli A, Hadid Y, Tzur S, Pereira L, Amorim A, Quintana-Murci L, Majamaa K, Herrnstadt C, Howell N, Balanovsky O, Kutuev I, Pshenichnov A, Gurwitz D, Bonne-Tamir B, Torroni A, Villems R, Skorecki K (Mar 2006).
"The matrilineal ancestry of Ashkenazi Jewry: portrait of a recent founder event" . American Journal of Human Genetics . 78 (3): 487–97.
doi :
10.1086/500307 .
PMC
1380291 .
PMID
16404693 .
van Holst Pellekaan SM, Ingman M, Roberts-Thomson J, Harding RM (Oct 2006). "Mitochondrial genomics identifies major haplogroups in Aboriginal Australians". American Journal of Physical Anthropology . 131 (2): 282–94.
doi :
10.1002/ajpa.20426 .
PMID
16596590 .