Reactome | Complex I biogenesis

Complex I biogenesis

Stable Identifier

R-HSA-6799198

DOI

10.3180/R-HSA-6799198.4

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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Complex I (NADH:ubiquinone oxidoreductase or NADH dehydrogenase) utilises NADH formed from glycolysis and the TCA cycle to pump protons out of the mitochondrial matrix. It is the largest enzyme complex in the electron transport chain, containing 11 core and 34 accessory subunits. Seven subunits (ND1-6, ND4L) are encoded by mitochondrial DNA, the remainder are encoded in the nucleus. The enzyme has a FMN prosthetic group and 8 Iron-Sulfur (Fe-S) clusters. The subunits are assembled together in a coordinated manner via preassembled subcomplexes to form the mature holoenzyme. At least 24 so-called "assembly factor" proteins, acting intrinsically or transiently, are required for constructing complex I although their exact roles in the biogenesis are not fully understood (Fernandez-Vizarra et al. 2009, Mckenzie & Ryan 2010, Mimaki et al. 2012, Andrews et al. 2013; reviewed by Laube et al., 2024).

Literature References

PubMed ID	Title	Journal	Year
21924235	Understanding mitochondrial complex I assembly in health and disease Wang, X, Ryan, MT, Thorburn, DR, McKenzie, M, Mimaki, M	Biochim. Biophys. Acta	2012
20552642	Assembly factors of human mitochondrial complex I and their defects in disease Ryan, MT, McKenzie, M	IUBMB Life	2010
38372588	Using cryo-EM to understand the assembly pathway of respiratory complex I Vonck, J, Schiller, J, Zickermann, V, Laube, E	Acta Crystallogr D Struct Biol	2024
24191001	Assembly factors for the membrane arm of human complex I Fearnley, IM, Carroll, J, Andrews, B, Walker, JE, Ding, S	Proc. Natl. Acad. Sci. U.S.A.	2013
16760263	Assembly of mitochondrial cytochrome c-oxidase, a complicated and highly regulated cellular process Soto, IC, Horn, D, Barrientos, A, Fontanesi, F	Am. J. Physiol., Cell Physiol.	2006