CHCHD4

CHCHD4, a component of human mitochondria, belongs to a protein family whose members share 6 highly conserved cysteine residues constituting a -CXC-CX(9)C-CX(9)C- motif in the C terminus (Hofmann et al., 2005 [PubMed 16185709]).[supplied by OMIM

Full Name

coiled-coil-helix-coiled-coil-helix domain containing 4

Function

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:26387864, PubMed:19182799, PubMed:21059946, PubMed:23186364, PubMed:23676665, 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).

Biological Process

de novo' posttranslational protein folding Source: UniProtKB
Mitochondrial respiratory chain complex assembly Source: UniProtKB
Peptidyl-cysteine oxidation Source: UniProtKB
Protein import into mitochondrial intermembrane space Source: UniProtKB
Protein maturation by protein folding Source: UniProtKB

Cellular Location

Mitochondrion intermembrane space

PTM

Forms intrachain disulfide bridges, but exists in different redox states.