Mitochondrial import inner membrane translocase subunit TIM14 (DNAJC19)

Mitochondrial import inner membrane translocase subunit TIM14 (DNAJC19) is a mitochondrial co-chaperone protein located in the inner mitochondrial membrane, where it participates in the ATP-dependent import of transit peptide-containing proteins from the cytosol into the mitochondrial matrix, primarily as part of the TIM23 complex. Unlike many other DNAJ family members, TIM14’s DNAJ domain is positioned at the C-terminus, and its transmembrane domain ensures membrane localization. TIM14 also complexes with prohibitins, regulating mitochondrial morphology and cardiolipin remodeling, a lipid crucial for mitochondrial membrane integrity and function. Loss of function mutations in DNAJC19 cause dilated cardiomyopathy with ataxia (DCMA) syndrome, consisting of severe cardiac and neurological manifestations, and is associated biochemically with mitochondrial fragmentation, abnormal cristae formation, increased reactive oxygen species, and altered metabolic flux in cardiac cells. The gene is located on human chromosome 3q26.33. Diagnostic markers include elevated 3-methylglutaconic acid and evidence of mitochondrial dysfunction. As of 2024, DNAJC19 is not a direct pharmacological target, but is of substantial interest for developing approaches to mitigate mitochondrial protein import deficiencies and related pathologies.

Other names

DNAJC19DnaJ heat shock protein family (Hsp40) member C19PAM18TIM14TIMM14DnaJ (Hsp40) homolog, subfamily C, member 19Homolog of yeast TIM14DnaJ-like protein subfamily C member 19

Not applicable; no approved drugs target DNAJC19 directly, but potential mechanisms for future modulators may include stabilization of mitochondrial import, chaperone activity modulation, or rescue of mitochondrial bioenergetics