DnaJ heat shock protein family member C15 (DNAJC15)

DnaJ heat shock protein family member C15 (DNAJC15) is a mitochondrial co-chaperone belonging to the Hsp40 (DnaJ) family, specifically the class C (DNAJC) subfamily[1]. It plays a central role in regulating protein import into the mitochondrial matrix via the TIM23 translocase complex and enables the activation of mitochondrial Hsp70 ATPase activity, contributing to proper mitochondrial bioenergetics and homeostasis[1]. DNAJC15 negatively regulates the mitochondrial respiratory chain by limiting ATP generation and preventing mitochondrial hyperpolarization[1]. Disease mutations in DNAJC15 are associated with metabolic disorders such as 3-methylglutaconic aciduria type V and spondyloepimetaphyseal dysplasia[1]. Differential expression or methylation of DNAJC15 has been implicated in chemotherapy resistance and carcinogenesis, particularly in ovarian and breast cancers[1]. The protein is considered a molecular chaperone rather than a receptor, enzyme, or transporter, and is characterized by the presence of a conserved J-domain that interacts with Hsp70 chaperones[1][3][4]. No approved drugs currently target DNAJC15 directly, and there are no known clinical biomarkers based on its modulation[1].

Other names

DNAJD1DJC15DNAJ homolog subfamily C member 15

Modulation of mitochondrial protein import machinery, Negative regulation of mitochondrial ATP generation by interacting with mitochondrial Hsp70/HSPA9, Regulation of mitochondrial membrane potential