Reactome | COX15 transforms heme O to heme A

COX15 transforms heme O to heme A

Stable Identifier

R-HSA-2995334

Type

Reaction [transition]

Species

Homo sapiens

Compartment

mitochondrial matrix, mitochondrial inner membrane

Synonyms

2 A + Fe(II)-heme o + H2O => 2 AH2 + Fe(II)-heme a

ReviewStatus

5/5

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Heme A is the prosthetic group of cytochrome c oxidase, the terminal enzyme in the respiratory chain. It is formed by the action of cytochrome c oxidase assembly protein COX15 homolog (COX15) on heme O, coupled to the conversion of an unknown hydrogen acceptor molecule to its cognate hydrogen donor (Petruzzella et al. 1998, Antonicka et al. 2003, Rivett et al. 2021). Defects in COX15 cause of mitochondrial complex IV deficiency (MT-C4D; MIM:220110), also called cytochrome c oxidase deficiency resulting in a disorder of the mitochondrial respiratory chain seen as heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs (Antonicka et al. 2003). Defects in COX15 also cause Leigh syndrome (LS; MIM:256000), an early-onset progressive neurodegenerative disorder characterised by the presence of focal, bilateral lesions in one or more areas of the central nervous system (Oquendo et al. 2004, Bugiani et al. 2005).

Literature References

PubMed ID	Title	Journal	Year
9878253	Identification and characterization of human cDNAs specific to BCS1, PET112, SCO1, COX15, and COX11, five genes involved in the formation and function of the mitochondrial respiratory chain Petruzzella, V, Ianna, P, Zeviani, M, Carrozzo, R, Fernandez, P, Tiranti, V	Genomics	1998
34428995	Biosynthesis and trafficking of heme o and heme a: new structural insights and their implications for reaction mechanisms and prenylated heme transfer Feig, M, Rivett, ED, Heo, L, Hegg, EL	Crit Rev Biochem Mol Biol	2021
15235026	Functional and genetic studies demonstrate that mutation in the COX15 gene can cause Leigh syndrome Brown, GK, Shoubridge, EA, Oquendo, CE, Reardon, W, Antonicka, H	J. Med. Genet.	2004
15863660	Novel mutations in COX15 in a long surviving Leigh syndrome patient with cytochrome c oxidase deficiency Zeviani, M, Uziel, G, Bugiani, M, Tiranti, V, Farina, L	J. Med. Genet.	2005
12474143	Mutations in COX15 produce a defect in the mitochondrial heme biosynthetic pathway, causing early-onset fatal hypertrophic cardiomyopathy Kennaway, NG, Carlson, CG, Antonicka, H, Hoffbuhr, KC, Mattman, A, Shoubridge, EA, Leary, SC, Glerum, DM	Am. J. Hum. Genet.	2003