TIMM44

Summary

Gene Symbol: TIMM44
Description: translocase of inner mitochondrial membrane 44
Alias: TIM44, mitochondrial import inner membrane translocase subunit TIM44, translocase of inner mitochondrial membrane 44 homolog
Species: human
Products:     TIMM44

Top Publications

  1. Liu Q, D Silva P, Walter W, Marszalek J, Craig E. Regulated cycling of mitochondrial Hsp70 at the protein import channel. Science. 2003;300:139-41 pubmed
    ..b>Tim44, a peripheral inner-membrane protein, tethers it to the import channel...
  2. Bauer M, Gempel K, Reichert A, Rappold G, Lichtner P, Gerbitz K, et al. Genetic and structural characterization of the human mitochondrial inner membrane translocase. J Mol Biol. 1999;289:69-82 pubmed
    ..cerevisiae, translocation of preproteins into the matrix requires the membrane proteins Tim23, Tim17 and Tim44, which drive translocation in cooperation with mtHsp70 and its co-chaperone Mge1p...
  3. Pareek G, Samaddar M, D Silva P. Primary sequence that determines the functional overlap between mitochondrial heat shock protein 70 Ssc1 and Ssc3 of Saccharomyces cerevisiae. J Biol Chem. 2011;286:19001-13 pubmed publisher
    ..The substrate-binding domain of Ssc3 showed poor affinity toward mitochondrial client proteins and Tim44 due to the open conformation in ADP-bound state...
  4. Ting S, Schilke B, Hayashi M, Craig E. Architecture of the TIM23 inner mitochondrial translocon and interactions with the matrix import motor. J Biol Chem. 2014;289:28689-96 pubmed publisher
    ..cross-linker in the matrix exposed loop between transmembrane domains 1 and 2 (loop 1) cross-linked to Tim44. Alterations in this loop destabilized interaction of Tim44 with the translocon...
  5. Smith J, Singha U, Misra S, Chaudhuri M. Divergent Small Tim Homologues Are Associated with TbTim17 and Critical for the Biogenesis of TbTim17 Protein Complexes in Trypanosoma brucei. mSphere. 2018;3: pubmed publisher
    ..brucei, and play an essential role in the stability of the TbTim17 complexes. Therefore, these divergent proteins are critical for mitochondrial protein biogenesis in T. brucei. ..
  6. Pantazopoulou A, Galmarini C, Peñalva M. Molecular basis of resistance to the microtubule-depolymerizing antitumor compound plocabulin. Sci Rep. 2018;8:8616 pubmed publisher
    ..two subunits of the eukaryotic translation initiation factor eIF2B activating the General Amino Acid Control, (2) TIM44, an essential component of the inner mitochondrial membrane translocase, (3) two transcription factors of the ..
  7. Miyata N, Tang Z, Conti M, Johnson M, Douglas C, Hasson S, et al. Adaptation of a Genetic Screen Reveals an Inhibitor for Mitochondrial Protein Import Component Tim44. J Biol Chem. 2017;292:5429-5442 pubmed publisher
    ..docking and molecular dynamics modeling revealed that MB-10 binds to a specific pocket in the C-terminal domain of Tim44 of the protein-associated motor (PAM) complex...
  8. Ting S, Yan N, Schilke B, Craig E. Dual interaction of scaffold protein Tim44 of mitochondrial import motor with channel-forming translocase subunit Tim23. elife. 2017;6: pubmed publisher
    ..Inward movement is driven by the matrix-localized, Hsp70-based motor. The scaffold Tim44, interacting with the matrix face of the translocon, recruits other motor subunits and binds incoming presequence...
  9. Banerjee R, Gladkova C, Mapa K, Witte G, Mokranjac D. Protein translocation channel of mitochondrial inner membrane and matrix-exposed import motor communicate via two-domain coupling protein. elife. 2015;4:e11897 pubmed publisher
    ..How these two processes are coordinated remained unclear. We show here that the two domain structure of Tim44 plays a central role in this process...

More Information

Publications22

  1. Martincová E, Voleman L, Pyrih J, Žárský V, Vondráčková P, Kolísko M, et al. Probing the Biology of Giardia intestinalis Mitosomes Using In Vivo Enzymatic Tagging. Mol Cell Biol. 2015;35:2864-74 pubmed publisher
    ..This approach enabled the identification of highly diverged mitosomal Tim44 (GiTim44), the first known component of the mitosomal inner membrane translocase (TIM)...
  2. 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. ..
  3. Sinha D, Joshi N, Chittoor B, Samji P, D Silva P. Role of Magmas in protein transport and human mitochondria biogenesis. Hum Mol Genet. 2010;19:1248-62 pubmed publisher
    ..Together, we propose a model showing how Magmas:DnaJC19 subcomplex is associated with TIM23 complex and thus regulates mitochondrial import process. ..
  4. Aguileta M, Korać J, Durcan T, Trempe J, Haber M, Gehring K, et al. The E3 ubiquitin ligase parkin is recruited to the 26 S proteasome via the proteasomal ubiquitin receptor Rpn13. J Biol Chem. 2015;290:7492-505 pubmed publisher
    ..However, it did delay the clearance of mitochondrial proteins (TIM23, TIM44, and TOM20) and enhance parkin autoubiquitination...
  5. Madamba S, Damri K, Dejean L, Peixoto P. Mitochondrial Ion Channels in Cancer Transformation. Front Oncol. 2015;5:120 pubmed publisher
    ..This mini review discusses how mitochondrial channels may be associated with cancer transformation and expands on the possible involvement of mitochondrial protein import complexes in pathophysiological process. ..
  6. Huang Y, Zhou J, Luo S, Wang Y, HE J, Luo P, et al. Identification of a fluorescent small-molecule enhancer for therapeutic autophagy in colorectal cancer by targeting mitochondrial protein translocase TIM44. Gut. 2018;67:307-319 pubmed publisher
    ..mass spectrometry and siRNA interference studies demonstrate that translocase of inner mitochondrial membrane 44 (TIM44)-superoxide dismutase 2 (SOD2) pathway inhibition is responsible for the excessive ROS, autophagy and apoptosis ..
  7. Moro F, Sirrenberg C, Schneider H, Neupert W, Brunner M. The TIM17.23 preprotein translocase of mitochondria: composition and function in protein transport into the matrix. EMBO J. 1999;18:3667-75 pubmed
    ..The components Tim17, Tim23 and Tim44 are present in this complex in equimolar amounts...
  8. Handa N, Kishishita S, Morita S, Akasaka R, Jin Z, Chrzas J, et al. Structure of the human Tim44 C-terminal domain in complex with pentaethylene glycol: ligand-bound form. Acta Crystallogr D Biol Crystallogr. 2007;63:1225-34 pubmed
    Familial oncocytic thyroid carcinoma is associated with a missense mutation, P308Q, in the C-terminal domain of Tim44. Tim44 is the mitochondrial inner-membrane translocase subunit and it functions as a membrane anchor for the ..
  9. Pais J, Schilke B, Craig E. Reevaluation of the role of the Pam18:Pam16 interaction in translocation of proteins by the mitochondrial Hsp70-based import motor. Mol Biol Cell. 2011;22:4740-9 pubmed publisher
  10. Yuryev A, Ono M, Goff S, Macaluso F, Wennogle L. Isoform-specific localization of A-RAF in mitochondria. Mol Cell Biol. 2000;20:4870-8 pubmed
    ..This information is discussed in view of the important role of mitochondria in cellular functions involving energy balance, proliferation, and apoptosis and the potential role of A-RAF in regulating these systems. ..
  11. Wang Y, Katayama A, Terami T, Han X, Nunoue T, Zhang D, et al. Translocase of inner mitochondrial membrane 44 alters the mitochondrial fusion and fission dynamics and protects from type 2 diabetes. Metabolism. 2015;64:677-88 pubmed publisher
    ..b>Timm44 is upregulated in the kidneys of streptozotocin-induced diabetic mice...
  12. Ozsvári B, Sotgia F, Lisanti M. A new mutation-independent approach to cancer therapy: Inhibiting oncogenic RAS and MYC, by targeting mitochondrial biogenesis. Aging (Albany NY). 2017;9:2098-2116 pubmed publisher
    ..In this context, we developed a new Myc-based Mito-Signature consisting of 3 mitochondrial genes (HSPD1; COX5B; TIMM44) for effectively predicting tumor recurrence (HR=4.69; p=2.4e-08) and distant metastasis (HR=4.94; p=2...
  13. Abbott W, Mellor A, Edwards Y, Feizi T. Soluble bovine galactose-binding lectin. cDNA cloning reveals the complete amino acid sequence and an antigenic relationship with the major encephalitogenic domain of myelin basic protein. Biochem J. 1989;259:283-90 pubmed
    ..In myelin basic protein the tetrapeptide is a part of the major domain previously shown to be responsible for the induction of experimental allergic encephalomyelitis. ..