Mitochondrial intermembrane space import and assembly protein 40 (Coiled-coil-helix-coiled-coil-helix domain-containing protein 4)
1_MSYCR 6_ QEGKD 11_ RIIFV 16_ TKEDH 21_ ETPSS 26_ AELVA 31_ DDPND 36_ PYEEH 41_ GLILP 46_ NGNIN 51_ WNCPC 56_ LGGMA 61_ SGPCG 66_ EQFKS 71_ AFSCF 76_ HYSTE 81_ EIKGS 86_ DCVDQ 91_ FRAMQ 96_ ECMQK 101_ YPDLY 106_ PQEDE 111_ DEEEE 116_ REKKP 121_ AEQAE 126_ ETAPI 131_ EATAT 136_KEEEG
1: Central component of a redox-sensitive mitochondrial intermembrane space import machinery which is required for the biogenesis of respiratory chain complexes (PubMed:26004228). Functions as chaperone and catalyzes the formation of disulfide bonds in substrate proteins, such as COX17, COX19, MICU1 and COA7 (PubMed:16185709, PubMed:19182799, PubMed:21059946, PubMed:23186364, PubMed:23676665, PubMed:26387864, PubMed:30885959). Required for the import and folding of small cysteine-containing proteins (small Tim) in the mitochondrial intermembrane space (IMS). Required for the import of COA7 in the IMS (PubMed:30885959). Precursor proteins to be imported into the IMS are translocated in their reduced form into the mitochondria. The oxidized form of CHCHD4/MIA40 forms a transient intermolecular disulfide bridge with the reduced precursor protein, resulting in oxidation of the precursor protein that now contains an intramolecular disulfide bond and is able to undergo folding in the IMS (PubMed:16185709, PubMed:19182799, PubMed:21059946, PubMed:23676665). Reduced CHCHD4/MIA40 is then reoxidized by GFER/ERV1 via a disulfide relay system (PubMed:23186364). Mediates formation of disulfide bond in MICU1 in the IMS, promoting formation of the MICU1-MICU2 heterodimer that regulates mitochondrial calcium uptake (PubMed:26387864)