Coiled-coil-helix-coiled-coil-helix domain-containing protein 5 (CHCHD5)

Coiled-coil-helix-coiled-coil-helix domain-containing protein 5 (CHCHD5) is a small mitochondrial protein of ~13 kDa located in the mitochondrial intermembrane space, characterized by a twin CX(9)C cysteine motif and two CHCH domains stabilized by disulfide bonds[1][4]. CHCHD5 acts as a substrate of the Mia40-dependent oxidative folding pathway, which is critical for mitochondrial protein import and the maintenance of redox balance[2][3]. Structurally, CHCHD5 contains two weakly interacting CHCH domains and adopts multiple conformations due to hydrophobic interactions; reduction of its disulfide bonds causes protein unfolding and aggregation[1][3][4]. Homologous to yeast Mic14, CHCHD5 functions in mitochondrial oxygen consumption, and genetic variation in the human CHCHD5 gene (particularly SNP rs3748024) is associated with increased risk of hypertension and obesity[2]. While implicated in mitochondrial physiology and as a genetic risk locus for metabolic syndromes[2], CHCHD5 is not currently considered a direct pharmacological or therapeutic target, nor are there known drugs that act upon it or clinical safety concerns attributed to its modulation.

Other names

C2orf9MGC11104MIC14MIX14mitochondrial intermembrane space cysteine motif protein of 14 kDa homolog (S. cerevisiae)CHTM1