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

Stable Identifier
Reaction [transition]
Homo sapiens
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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

Damoiseaux, R, Teitell, MA, Douglas, CJ, Koehler, CM, Dabir, DV, Setoguchi, K, Hasson, SA, Zimmerman, J, Wongkongkathep, P, Johnson, ME

Dev. Cell 2013
19409522 The mitochondrial disulfide relay system protein GFER is mutated in autosomal-recessive myopathy with cataract and combined respiratory-chain deficiency

Ferrero, I, Bresolin, N, Tigano, M, Ronchi, D, Fassone, E, Donadoni, C, Saladino, F, Fortunato, F, Napoli, L, Salani, S, Lodi, T, Di Fonzo, A, Lamperti, C, Nizzardo, M, Bordoni, A, Moggio, M, Comi, GP, Corti, S

Am J Hum Genet 2009
19453276 Multiple pathways for mitochondrial protein traffic

Yamano, K, Endo, T

Biol Chem 2009
18174896 Multiple pathways for sorting mitochondrial precursor proteins

Pfanner, N, Wagner, R, Sickmann, A, Bolender, N, Meisinger, C

EMBO Rep 2008
15683237 Augmenter of liver regeneration: a flavin-dependent sulfhydryl oxidase with cytochrome c reductase activity

Thorpe, C, Farrell, SR

Biochemistry 2005
16185709 Functional and mutational characterization of human MIA40 acting during import into the mitochondrial intermembrane space

Hofmann, S, Baiker, K, Hell, K, Rothbauer, U, M├╝hlenbein, N, 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

Bahnson, BJ, Thorpe, C, Daithankar, VN, Schaefer, SA, Dong, M

Biochemistry 2010
25315652 MNRR1 (formerly CHCHD2) is a bi-organellar regulator of mitochondrial metabolism

Bai, M, Grossman, LI, Lee, I, Aras, S, H├╝ttemann, M, Springett, R

Mitochondrion 2015
Catalyst Activity

protein-disulfide reductase activity of MIA40:ERV1 [mitochondrial intermembrane space]

Inferred From
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