Reactome | MIA40:ERV1 (CHCHD4:GFER) oxidizes cysteine residues to cystine disulfide bonds

MIA40:ERV1 (CHCHD4:GFER) oxidizes cysteine residues to cystine disulfide bonds

Stable Identifier

R-HSA-1307802

Type

Reaction [transition]

Species

Homo sapiens

Compartment

mitochondrial intermembrane space

ReviewStatus

5/5

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MIA40:ERV1 (CHCHD4:GFER) oxidizes cysteine residues to cystine disulfide bonds

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Proteins are imported into the intermembrane space via the interaction between cysteine residues on the imported protein and CHCHD4 (MIA40 in yeast), which functions as a receptor to mediate translocation across the outer membrane. As inferred from the yeast MIA40:ERV1 complex, human CHCHD4 (MIA40 homolog) catalyzes the oxidation of cysteine residues in precursor proteins in the intermembrane space to form cystine bonds. The electrons from the cysteine residues are transferred to CHCHD4, then to GFER (ERV1 in yeast), and eventually to the respiratory chain. The interaction between yeast MIA40 and ERV1 is transitory.
In yeast, experimentally verified substrates of MIA40:ERV1 include COX17, COX19, CMC2, CMC3, CMC4, TIM13 (TIMM13 in human), TIM9 (TIMM9 in human), TIM10 (TIMM10 in human), CCS1 (CCS in human), TIM8 (TIMM8 in human), and ERV1 (GFER in human). Many other mitochondrial proteins are anticipated to be substrates of the MIA40:ERV1 complex.

Literature References

PubMed ID	Title	Journal	Year
23597483	A small molecule inhibitor of redox-regulated protein translocation into mitochondria Dabir, DV, Hasson, SA, Setoguchi, K, Johnson, ME, Wongkongkathep, P, Douglas, CJ, Zimmerman, J, Damoiseaux, R, Teitell, MA, Koehler, CM	Dev. Cell	2013
19409522	The mitochondrial disulfide relay system protein GFER is mutated in autosomal-recessive myopathy with cataract and combined respiratory-chain deficiency Di Fonzo, A, Ronchi, D, Lodi, T, Fassone, E, Tigano, M, Lamperti, C, Corti, S, Bordoni, A, Fortunato, F, Nizzardo, M, Napoli, L, Donadoni, C, Salani, S, Saladino, F, Moggio, M, Bresolin, N, Ferrero, I, Comi, GP	Am J Hum Genet	2009
19453276	Multiple pathways for mitochondrial protein traffic Endo, T, Yamano, K	Biol Chem	2009
18174896	Multiple pathways for sorting mitochondrial precursor proteins Bolender, N, Sickmann, A, Wagner, R, Meisinger, C, Pfanner, N	EMBO Rep	2008
15683237	Augmenter of liver regeneration: a flavin-dependent sulfhydryl oxidase with cytochrome c reductase activity Farrell, SR, Thorpe, C	Biochemistry	2005
16185709	Functional and mutational characterization of human MIA40 acting during import into the mitochondrial intermembrane space Hofmann, S, Rothbauer, U, Mühlenbein, N, Baiker, K, Hell, K, Bauer, MF	J Mol Biol	2005
20593814	Structure of the human sulfhydryl oxidase augmenter of liver regeneration and characterization of a human mutation causing an autosomal recessive myopathy Daithankar, VN, Schaefer, SA, Dong, M, Bahnson, BJ, Thorpe, C	Biochemistry	2010
25315652	MNRR1 (formerly CHCHD2) is a bi-organellar regulator of mitochondrial metabolism Aras, S, Bai, M, Lee, I, Springett, R, Hüttemann, M, Grossman, LI	Mitochondrion	2015