DNAJC19

Mitochondrial import inner membrane translocase subunit TIM14 is an is_associated_with::enzyme that in humans is encoded by the DNAJC19 is_associated_with::gene. TIM14 belongs to the DnaJ family, which has been involved in Hsp40/Hsp70 chaperone systems. As a is_associated_with::mitochondrial chaperone, TIM14 functions as part of the TIM23 complex import motor to facilitate the import of nuclear-encoded proteins into the mitochondria. TIM14 also complexes with is_associated_with::prohibitin complexes to regulate mitochondrial is_associated_with::morphogenesis, and has been implicated in is_associated_with::dilated cardiomyopathy with ataxia.

Function
TIM14 is required for the ATP-dependent import of mitochondrial pre-proteins into the is_associated_with::mitochondrial matrix.The J-domain of TIM14 stimulates mtHsp70 is_associated_with::ATPase activity to power this transport.

Additionally, TIM14 helps regulate mitochondrial morphology by complexing with prohibitins to perform disphosphoglycerolipid is_associated_with::cardiolipin (CL) remodeling. CL is a key is_associated_with::phospholipid in mitochondrial membranes that modulates the fusion and fission of mitochondrial membranes, as well as is_associated_with::mitophagy and is_associated_with::apoptosis.

Clinical significance
Defects in DNAJC19 have been observed primarily in cases of is_associated_with::dilated cardiomyopathy with ataxia (DCMA), though it has also been associated with is_associated_with::growth failure, is_associated_with::microcytic anemia, and male genital anomalies. DNAJC19 was first implicated in DCMA in a study on the consanguineous Hutterite population, which has since been confirmed in other European populations. In the clinic, DNAJC19 mutations can be detected by screening for elevated levels of is_associated_with::3-methylglutaconic acid, mitochondrial distress, dilated cardiomyopathy, prolongation of the is_associated_with::QT interval in the is_associated_with::electrocardiogram, and is_associated_with::cerebellar ataxia.

Interactions
TIM14 interacts with:
 * is_associated_with::TIMM44,
 * mtHsp70,
 * TIMM16/is_associated_with::PAM16, and
 * is_associated_with::PHB2.