Reactome | Complex IV assembly

Complex IV assembly

Stable Identifier

R-HSA-9864848

DOI

10.3180/R-HSA-9864848.1

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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At least 30 proteins are required to form the functional human complex IV, 14 of which are complex subunits. The complex contains the cofactors heme a, heme a3, and one mononuclear copper (CuB) center in the COX1 subunit, and a binuclear copper (CuA) in COX2, as well as several lipid molecules (phosphatidylethanolamine, PE, cardiolipin, CL) in different subunits (PDB 5Z62; Zong et al., 2018). The insertion of these cofactors is an intricate process requiring many assembly factors (Nývltová et al, 2022; reviewed in Mick et al., 2011; Timón-Gómez et al., 2018; Watson & McStay, 2020; Dennerlein et al., 2023).

Mutations in any complex IV subunits or assembly factors lead to different types of complex IV deficiency, usually manifesting as Leigh syndrome (MIM:220110; reviewed in Pecina et al., 2004; Čunátová et al., 2020)

Literature References

PubMed ID	Title	Journal	Year
35750769	Coordination of metal center biogenesis in human cytochrome c oxidase Nývltová, E, Dietz, JV, Seravalli, J, Khalimonchuk, O, Barrientos, A	Nat Commun	2022
28870773	Mitochondrial cytochrome c oxidase biogenesis: Recent developments Timón-Gómez, A, Nývltová, E, Abriata, LA, Vila, AJ, Hosler, J, Barrientos, A	Semin Cell Dev Biol	2018
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
21179059	Inventory control: cytochrome c oxidase assembly regulates mitochondrial translation Mick, DU, Fox, TD, Rehling, P	Nat Rev Mol Cell Biol	2011
33008142	Functions of Cytochrome c oxidase Assembly Factors Watson, SA, McStay, GP	Int J Mol Sci	2020
15119951	Genetic defects of cytochrome c oxidase assembly Pecina, P, Houstková, H, Hansikova, H, Zeman, J, Houstek, J	Physiol Res	2004
37247261	Cytochrome c oxidase biogenesis - from translation to early assembly of the core subunit COX1 Dennerlein, S, Rehling, P, Richter-Dennerlein, R	FEBS Lett	2023
30030519	Structure of the intact 14-subunit human cytochrome c oxidase Zong, S, Wu, M, Gu, J, Liu, T, Guo, R, Yang, M	Cell Res	2018