Gene Symbol: TIMM50
Description: translocase of inner mitochondrial membrane 50
Alias: MGCA9, TIM50, TIM50L, mitochondrial import inner membrane translocase subunit TIM50, Tim50-like protein, homolog of yeast Tim50
Species: human
Products:     TIMM50

Top Publications

  1. Guo Y, Cheong N, Zhang Z, De Rose R, Deng Y, Farber S, et al. Tim50, a component of the mitochondrial translocator, regulates mitochondrial integrity and cell death. J Biol Chem. 2004;279:24813-25 pubmed
    In yeast, Tim50 along with Tim23 regulate translocation of presequence-containing proteins across the mitochondrial inner membrane...
  2. Dayan D, Bandel M, Gunsel U, Nussbaum I, Prag G, Mokranjac D, et al. A mutagenesis analysis of Tim50, the major receptor of the TIM23 complex, identifies regions that affect its interaction with Tim23. Sci Rep. 2019;9:2012 pubmed publisher
    ..b>Tim50 is the central receptor of the complex that recognizes precursor proteins in the IMS...
  3. Bose H, Gebrail F, Marshall B, Perry E, Whittal R. Inner Mitochondrial Translocase Tim50 Is Central in Adrenal and Testicular Steroid Synthesis. Mol Cell Biol. 2019;39: pubmed publisher
    ..of the SCC C terminus into the TIM23 complex, amino acids 141 to 146 interact with the intermembrane-exposed Tim50 protein, forming a large complex. The absence of Tim50 or its mutation reduced enzymatic activity...
  4. Thomas J, Bose H. Regulation of human 3-beta-hydroxysteroid dehydrogenase type-2 (3βHSD2) by molecular chaperones and the mitochondrial environment affects steroidogenesis. J Steroid Biochem Mol Biol. 2015;151:74-84 pubmed publisher
    ..3βHSD2 interacts with the mitochondrial translocase, Tim50, to regulate progesterone and androstenedione formation...
  5. Bajaj R, Jaremko Å, Jaremko M, Becker S, Zweckstetter M. Molecular basis of the dynamic structure of the TIM23 complex in the mitochondrial intermembrane space. Structure. 2014;22:1501-11 pubmed publisher
    ..spectroscopy, we characterized the dynamic interaction network of the intermembrane space domains of Tim23, Tim21, Tim50, and Tom22 at single-residue level...
  6. Mokranjac D, Sichting M, Popov Celeketic D, Mapa K, Gevorkyan Airapetov L, Zohary K, et al. Role of Tim50 in the transfer of precursor proteins from the outer to the inner membrane of mitochondria. Mol Biol Cell. 2009;20:1400-7 pubmed publisher
    ..Here, we have analyzed Tim50, a subunit of the TIM23 complex that is implicated in transfer of precursors from TOM to TIM23...
  7. Reyes A, Melchionda L, Burlina A, Robinson A, Ghezzi D, Zeviani M. Mutations in TIMM50 compromise cell survival in OxPhos-dependent metabolic conditions. EMBO Mol Med. 2018;10: pubmed publisher
    b>TIMM50 is an essential component of the TIM23 complex, the mitochondrial inner membrane machinery that imports cytosolic proteins containing a mitochondrial targeting presequence into the mitochondrial inner compartment...
  8. Schulz C, Schendzielorz A, Rehling P. Unlocking the presequence import pathway. Trends Cell Biol. 2015;25:265-75 pubmed publisher
    ..Recognition of the presequence by Tim50 triggers rearrangements of the presequence translocase, priming it for inner membrane translocation...
  9. Fullerton M, Singha U, Duncan M, Chaudhuri M. Down regulation of Tim50 in Trypanosoma brucei increases tolerance to oxidative stress. Mol Biochem Parasitol. 2015;199:9-18 pubmed publisher
    ..We recently characterized a homolog of the translocase of the mitochondrial inner membrane, Tim50, in T. brucei...

More Information


  1. Opalińska M, Parys K, Murcha M, Janska H. The plant i-AAA protease controls the turnover of an essential mitochondrial protein import component. J Cell Sci. 2018;131: pubmed publisher
    ..the abundance of the Tim17-2 protein, an essential component of the TIM17:23 translocase (Tim17-2 together with Tim50 and Tim23), is directly controlled by the proteolytic activity of FTSH4...
  2. Schendzielorz A, Schulz C, Lytovchenko O, Clancy A, Guiard B, Ieva R, et al. Two distinct membrane potential-dependent steps drive mitochondrial matrix protein translocation. J Cell Biol. 2017;216:83-92 pubmed publisher
    ..The presequence translocase constituent Pam17 is specifically recruited by the receptor Tim50 to promote the transport of hypersensitive precursors into the matrix...
  3. Li J, Sha B. The structure of Tim50(164-361) suggests the mechanism by which Tim50 receives mitochondrial presequences. Acta Crystallogr F Struct Biol Commun. 2015;71:1146-51 pubmed publisher
    Mitochondrial preproteins are transported through the translocase of the outer membrane (TOM) complex. Tim50 and Tim23 then transfer preproteins with N-terminal targeting presequences through the intermembrane space (IMS) across the ..
  4. Zhang Y, Xu Y, Zhao Q, Ji Z, Li Q, Li S. Expression and structural characterization of human translocase of inner membrane of mitochondria Tim50. Protein Expr Purif. 2011;80:130-7 pubmed publisher
    ..b>Tim50 is a major receptor in TIM23 complex, which spans the inner membrane with a single transmembrane segment and ..
  5. Tang K, Zhao Y, Li H, Zhu M, Li W, Liu W, et al. Translocase of Inner Membrane 50 Functions as a Novel Protective Regulator of Pathological Cardiac Hypertrophy. J Am Heart Assoc. 2017;6: pubmed publisher
    Translocase of inner membrane 50 (TIM50) is a member of the translocase of inner membrane (TIM) complex in the mitochondria...
  6. Schusdziarra C, Blamowska M, Azem A, Hell K. Methylation-controlled J-protein MCJ acts in the import of proteins into human mitochondria. Hum Mol Genet. 2013;22:1348-57 pubmed publisher
    ..In summary, our results show that MCJ functions as J co-chaperone of the human TIM23 pre-protein translocase, suggesting a link between mitochondrial pre-protein import and tumorigenesis. ..
  7. Yuryev A, Wennogle L. Novel raf kinase protein-protein interactions found by an exhaustive yeast two-hybrid analysis. Genomics. 2003;81:112-25 pubmed
    ..We propose possible functional consequences of these novel Raf interactions. ..
  8. Cui H, Schlesinger J, Schoenhals S, Tönjes M, Dunkel I, Meierhofer D, et al. Phosphorylation of the chromatin remodeling factor DPF3a induces cardiac hypertrophy through releasing HEY repressors from DNA. Nucleic Acids Res. 2016;44:2538-53 pubmed publisher
    ..Thus, we present a novel pathway for pathological cardiac hypertrophy, whose inhibition is a long-term therapeutic goal for the treatment of the course of heart failure. ..
  9. Zhang Y, Deng H, Zhang X, Li S. Interaction of divalent metal ions with human translocase of inner membrane of mitochondria Tim50. Biochem Biophys Res Commun. 2012;428:365-70 pubmed publisher
    ..b>Tim50 is a major receptor for transporting the precursor protein across the mitochondrial inner membrane in TIM23 ..
  10. Sankala H, Vaughan C, Wang J, Deb S, Graves P. Upregulation of the mitochondrial transport protein, Tim50, by mutant p53 contributes to cell growth and chemoresistance. Arch Biochem Biophys. 2011;512:52-60 pubmed publisher
    ..The protein, translocator of the inner mitochondrial membrane 50 (Tim50), was upregulated in a non-small cell lung carcinoma cell line (H1299) that expressed the p53 mutants R175H and ..
  11. Gao S, Sun H, Jiang H, Li L, Hu X, Xu X, et al. Loss of TIM50 suppresses proliferation and induces apoptosis in breast cancer. Tumour Biol. 2016;37:1279-87 pubmed publisher
    b>TIM50 is an essential component of TIM23 complex and involved in protein translocating into the inner mitochondrial membrane. Here, we found that TIM50 was increased in breast cancer cells by SILAC...
  12. Shahrour M, Staretz Chacham O, Dayan D, Stephen J, Weech A, Damseh N, et al. Mitochondrial epileptic encephalopathy, 3-methylglutaconic aciduria and variable complex V deficiency associated with TIMM50 mutations. Clin Genet. 2017;91:690-696 pubmed publisher
    ..Recently a homozygous mutation, Gly372Ser, in the TIMM50 gene, was reported in an abstract form, in three sibs who suffered from intractable epilepsy and developmental ..
  13. Xu H, Somers Z, Robinson M, Hebert M. Tim50a, a nuclear isoform of the mitochondrial Tim50, interacts with proteins involved in snRNP biogenesis. BMC Cell Biol. 2005;6:29 pubmed
    ..In this report, we identify a minor isoform of the mitochondrial Tim50, Tim50a, as a coilin interacting protein...
  14. Pawlak K, Prasad M, Thomas J, Whittal R, Bose H. Inner mitochondrial translocase Tim50 interacts with 3?-hydroxysteroid dehydrogenase type 2 to regulate adrenal and gonadal steroidogenesis. J Biol Chem. 2011;286:39130-40 pubmed publisher
    ..gradient ultracentrifugation, we show that that 3?HSD2 formed a transient association with the translocases Tim50 and Tom22 and with Tim23...
  15. Zheng G, Yang Y. ZNF76, a novel transcriptional repressor targeting TATA-binding protein, is modulated by sumoylation. J Biol Chem. 2004;279:42410-21 pubmed
    ..These results suggest that ZNF76 functions as a transcriptional repressor through its interaction with TBP and that sumoylation modulates its transcriptional repression activity. ..
  16. Yamamoto H, Esaki M, Kanamori T, Tamura Y, Nishikawa S, Endo T. Tim50 is a subunit of the TIM23 complex that links protein translocation across the outer and inner mitochondrial membranes. Cell. 2002;111:519-28 pubmed
    Based on the results of site-specific photocrosslinking of translocation intermediates, we have identified Tim50, a component of the yeast TIM23 import machinery, which mediates translocation of presequence-containing proteins across the ..
  17. Zhang Y, Deng H, Zhao Q, Li S. Interaction of presequence with human translocase of the inner membrane of mitochondria Tim50. J Phys Chem B. 2012;116:2990-8 pubmed publisher
    ..b>Tim50 is a major receptor for transporting the precursor protein across the mitochondrial inner membrane in the TIM23 ..