Reactome | MT-CO1 and MT-CO2 complexes associate, installing heme moieties

MT-CO1 and MT-CO2 complexes associate, installing heme moieties

Stable Identifier

R-HSA-9865579

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

mitochondrial inner membrane

ReviewStatus

5/5

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MT-CO1 and MT-CO2 complexes associate, installing heme moieties

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Both MT-CO1 and MT-CO2 pre-assembly complexes bind together, simultaneously installing heme moieties and associating with the COX7B, COX7C, and COX8A subunits. The assembly of catalytic metal redox centers (heme and copper) at MT-CO1 and MT-CO2 subunits of Complex IV must be coordinated because the accumulation of heme-containing Complex IV assembly intermediates lacking copper induces oxidative-stress mediated cytotoxicity. A dynamic metallochaperone complex involving the heme A biosynthetic enzymes COX10 and COX15, together with COX2-specific copper chaperones COA6, SCO1, and SCO2, catalyzes the insertion of two heme molecules into the MT-CO1 subunit, and one heme into the MT-CO2 subunit (Pacheu-Grau et al., 2015; Nývltová et al., 2022; reviewed in Čunátová et al., 2020; Rivett et al., 2021). The exact mechanism remains unclear, but the SURF1 subunit of MITRAC may act as an additional chaperone, for which there is evidence in bacterial models (Smith et al., 2005; Bundschuh et al., 2009). Mutations in SURF1 lead to complex IV deficiency (Zhu et al., 1998).

Literature References

PubMed ID	Title	Journal	Year
9843204	SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome Zhu, Z, Yao, J, Johns, T, Fu, K, De Bie, I, Macmillan, C, Cuthbert, AP, Newbold, RF, Wang, J, Chevrette, M, Brown, GK, Brown, RM, Shoubridge, EA	Nat Genet	1998
15764605	Assembly of cytochrome-c oxidase in the absence of assembly protein Surf1p leads to loss of the active site heme Smith, D, Gray, J, Mitchell, L, Antholine, WE, Hosler, JP	J Biol Chem	2005
19625251	Surf1, associated with Leigh syndrome in humans, is a heme-binding protein in bacterial oxidase biogenesis Bundschuh, FA, Hannappel, A, Anderka, O, Ludwig, B	J Biol Chem	2009
25959673	Cooperation between COA6 and SCO2 in COX2 maturation during cytochrome c oxidase assembly links two mitochondrial cardiomyopathies Pacheu-Grau, D, Bareth, B, Dudek, J, Juris, L, Vögtle, FN, Wissel, M, Leary, SC, Dennerlein, S, Rehling, P, Deckers, M	Cell Metab.	2015
34428995	Biosynthesis and trafficking of heme o and heme a: new structural insights and their implications for reaction mechanisms and prenylated heme transfer Rivett, ED, Heo, L, Feig, M, Hegg, EL	Crit Rev Biochem Mol Biol	2021
33129245	Role of cytochrome c oxidase nuclear-encoded subunits in health and disease Čunátová, K, Reguera, DP, Houstek, J, Mráček, T, Pecina, P	Physiol Res	2020