Mitochondrial import inner membrane translocase subunit TIM14 is an enzyme that in humans is encoded by the DNAJC19gene on chromosome 3. TIM14 belongs to the DnaJ family, which has been involved in Hsp40/Hsp70 chaperone systems. As a mitochondrialchaperone, 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 prohibitin complexes to regulate mitochondrial morphogenesis, and has been implicated in dilated cardiomyopathy with ataxia.
The protein encoded by the DNAJC19 gene possesses an unusual structure compared to the rest of the DNAJ protein family. Notably, the DNAJ domain of TIM14 is located at the C-terminal rather than the N-terminal, and the transmembrane domain confers membrane-bound localization for TIM14 while other DNAJ proteins are cytosolic. TIM14 orthologs in other species, such as the yeast Tim14 and Mdj2p proteins, confirm localization to the mitochondrial inner membrane.
TIM14 is required for the ATP-dependent import of mitochondrial pre-proteins into the mitochondrial matrix.The J-domain of TIM14 stimulates mtHsp70ATPase activity to power this transport.
Additionally, TIM14 helps regulate mitochondrial morphology by complexing with prohibitins to perform disphosphoglycerolipid cardiolipin (CL) remodeling. CL is a key phospholipid in mitochondrial membranes that modulates the fusion and fission of mitochondrial membranes, as well as mitophagy and apoptosis.
^ abcRichter-Dennerlein R, Korwitz A, Haag M, Tatsuta T, Dargazanli S, Baker M, Decker T, Lamkemeyer T, Rugarli EI, Langer T (Jul 2014). "DNAJC19, a mitochondrial cochaperone associated with cardiomyopathy, forms a complex with prohibitins to regulate cardiolipin remodeling". Cell Metabolism. 20 (1): 158–71. doi:10.1016/j.cmet.2014.04.016. PMID24856930.
^ abOjala T, Polinati P, Manninen T, Hiippala A, Rajantie J, Karikoski R, Suomalainen A, Tyni T (Oct 2012). "New mutation of mitochondrial DNAJC19 causing dilated and noncompaction cardiomyopathy, anemia, ataxia, and male genital anomalies". Pediatric Research. 72 (4): 432–7. doi:10.1038/pr.2012.92. PMID22797137.
^Mokranjac D, Bourenkov G, Hell K, Neupert W, Groll M (Oct 2006). "Structure and function of Tim14 and Tim16, the J and J-like components of the mitochondrial protein import motor". The EMBO Journal. 25 (19): 4675–85. doi:10.1038/sj.emboj.7601334. PMID16977310.
Sparkes R, Patton D, Bernier F (Apr 2007). "Cardiac features of a novel autosomal recessive dilated cardiomyopathic syndrome due to defective importation of mitochondrial protein". Cardiology in the Young. 17 (2): 215–7. doi:10.1017/S1047951107000042. PMID17244376.
Taylor SW, Fahy E, Zhang B, Glenn GM, Warnock DE, Wiley S, Murphy AN, Gaucher SP, Capaldi RA, Gibson BW, Ghosh SS (Mar 2003). "Characterization of the human heart mitochondrial proteome". Nature Biotechnology. 21 (3): 281–6. doi:10.1038/nbt793. PMID12592411.