CHCHD4
Description
The CHCHD4 (coiled-coil-helix-coiled-coil-helix domain containing 4) is a protein-coding gene located on chromosome 3.
CHCHD4 is a central component of a redox-sensitive mitochondrial intermembrane space import machinery that is required for the biogenesis of respiratory chain complexes. It acts as a chaperone and catalyzes the formation of disulfide bonds in substrate proteins like COX17, COX19, MICU1, and COA7, contributing to their folding and import into the mitochondrial intermembrane space (IMS). CHCHD4 plays a crucial role in the import and folding of small cysteine-containing proteins (small Tim) within the IMS. It also facilitates the import of COA7 into the IMS. During import, precursor proteins are initially translocated in their reduced form into the mitochondria. Oxidized CHCHD4 forms transient disulfide bridges with the reduced precursor proteins, leading to their oxidation and the formation of an intramolecular disulfide bond. This allows the precursor protein to fold within the IMS. Reduced CHCHD4 is then reoxidized by GFER/ERV1 through a disulfide relay system. CHCHD4 is involved in the formation of disulfide bonds in MICU1 within the IMS, promoting the formation of the MICU1-MICU2 heterodimer that regulates mitochondrial calcium uptake.
CHCHD4 is also known as MIA40, TIMM40.
