TIM50

Summary

Gene Symbol: TIM50
Description: protein translocase subunit TIM50
Alias: protein translocase subunit TIM50
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Geissler A, Chacinska A, Truscott K, Wiedemann N, Brandner K, Sickmann A, et al. The mitochondrial presequence translocase: an essential role of Tim50 in directing preproteins to the import channel. Cell. 2002;111:507-18 pubmed
    ..We have identified the essential protein Tim50, which exposes its major domain to the intermembrane space...
  2. Alder N, Sutherland J, Buhring A, Jensen R, Johnson A. Quaternary structure of the mitochondrial TIM23 complex reveals dynamic association between Tim23p and other subunits. Mol Biol Cell. 2008;19:159-70 pubmed
    ..These structural changes reveal that the macromolecular arrangement within the TIM23 complex is dynamic and varies with the physiological state of the mitochondrion. ..
  3. van der Laan M, Wiedemann N, Mick D, Guiard B, Rehling P, Pfanner N. A role for Tim21 in membrane-potential-dependent preprotein sorting in mitochondria. Curr Biol. 2006;16:2271-6 pubmed
    ..These findings suggest a new coupling mechanism in an energy-transducing membrane. ..
  4. Sanjuán Szklarz L, Guiard B, Rissler M, Wiedemann N, Kozjak V, van der Laan M, et al. Inactivation of the mitochondrial heat shock protein zim17 leads to aggregation of matrix hsp70s followed by pleiotropic effects on morphology and protein biogenesis. J Mol Biol. 2005;351:206-18 pubmed
  5. Schiller D, Cheng Y, Liu Q, Walter W, Craig E. Residues of Tim44 involved in both association with the translocon of the inner mitochondrial membrane and regulation of mitochondrial Hsp70 tethering. Mol Cell Biol. 2008;28:4424-33 pubmed publisher
  6. Dienhart M, Stuart R. The yeast Aac2 protein exists in physical association with the cytochrome bc1-COX supercomplex and the TIM23 machinery. Mol Biol Cell. 2008;19:3934-43 pubmed publisher
    ..The physiological implications of the association of AAC with the cytochrome bc(1)-COX-TIM23 supercomplex are also discussed. ..
  7. 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...
  8. Meinecke M, Wagner R, Kovermann P, Guiard B, Mick D, Hutu D, et al. Tim50 maintains the permeability barrier of the mitochondrial inner membrane. Science. 2006;312:1523-6 pubmed
    ..We found that the intermembrane space domain of Tim50 induced the Tim23 channel to close. Presequences overcame this effect and activated the channel for translocation...
  9. van der Laan M, Chacinska A, Lind M, Perschil I, Sickmann A, Meyer H, et al. Pam17 is required for architecture and translocation activity of the mitochondrial protein import motor. Mol Cell Biol. 2005;25:7449-58 pubmed
    ..Our findings suggest that Pam17 is required for the correct organization of the Pam16-Pam18 complex and thus contributes to regulation of mtHsp70 activity at the inner membrane translocation site. ..

More Information

Publications39

  1. Yamamoto H, Itoh N, Kawano S, Yatsukawa Y, Momose T, Makio T, et al. Dual role of the receptor Tom20 in specificity and efficiency of protein import into mitochondria. Proc Natl Acad Sci U S A. 2011;108:91-6 pubmed publisher
    ..Therefore Tom20 has a dual role in protein import into mitochondria: recognition of the targeting signal in the presequence and tethering the presequence to the TOM40 complex to increase import efficiency...
  2. Marom M, Dayan D, Demishtein Zohary K, Mokranjac D, Neupert W, Azem A. Direct interaction of mitochondrial targeting presequences with purified components of the TIM23 protein complex. J Biol Chem. 2011;286:43809-15 pubmed publisher
    ..The interaction of three different presequences with purified soluble domains of yeast Tim50 (Tim50IMS), Tim23 (Tim23IMS), and full-length Tim44 was examined...
  3. Chacinska A, Lind M, Frazier A, Dudek J, Meisinger C, Geissler A, et al. Mitochondrial presequence translocase: switching between TOM tethering and motor recruitment involves Tim21 and Tim17. Cell. 2005;120:817-29 pubmed
    ..Thus, the presequence translocase is not a static complex but switches between TOM tethering and PAM binding in a reaction cycle involving Tim21 and Tim17. ..
  4. Frazier A, Dudek J, Guiard B, Voos W, Li Y, Lind M, et al. Pam16 has an essential role in the mitochondrial protein import motor. Nat Struct Mol Biol. 2004;11:226-33 pubmed
    ..Thus, Pam16 is a newly identified type of motor subunit and is required to promote a functional PAM reaction cycle, thereby driving preprotein import into the matrix. ..
  5. Qian X, Gebert M, Höpker J, Yan M, Li J, Wiedemann N, et al. Structural basis for the function of Tim50 in the mitochondrial presequence translocase. J Mol Biol. 2011;411:513-9 pubmed publisher
    ..b>Tim50 and Tim23 transfer preproteins through the intermembrane space to the inner membrane...
  6. Hutu D, Guiard B, Chacinska A, Becker D, Pfanner N, Rehling P, et al. Mitochondrial protein import motor: differential role of Tim44 in the recruitment of Pam17 and J-complex to the presequence translocase. Mol Biol Cell. 2008;19:2642-9 pubmed publisher
    ..We suggest that Tim44 is not simply a scaffold for binding of motor subunits but plays a differential role in the recruitment of PAM modules to the inner membrane translocase. ..
  7. Gevorkyan Airapetov L, Zohary K, Popov Celeketic D, Mapa K, Hell K, Neupert W, et al. Interaction of Tim23 with Tim50 Is essential for protein translocation by the mitochondrial TIM23 complex. J Biol Chem. 2009;284:4865-72 pubmed publisher
    ..Tim23 and Tim50, two essential proteins of the complex, expose conserved domains into the intermembrane space that interact with ..
  8. 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 ..
  9. D Silva P, Schilke B, Hayashi M, Craig E. Interaction of the J-protein heterodimer Pam18/Pam16 of the mitochondrial import motor with the translocon of the inner membrane. Mol Biol Cell. 2008;19:424-32 pubmed
    ..These data suggest a model in which Tim44 serves as a scaffold for precise positioning of mtHsp70 and its cochaperone Pam18 at the translocon. ..
  10. Tamura Y, Harada Y, Yamano K, Watanabe K, Ishikawa D, Ohshima C, et al. Identification of Tam41 maintaining integrity of the TIM23 protein translocator complex in mitochondria. J Cell Biol. 2006;174:631-7 pubmed
    ..These results suggest that Tam41 facilitates mitochondrial protein import by maintaining the functional integrity of the TIM23 protein translocator complex from the matrix side of the inner membrane. ..
  11. Popov Celeketic D, Mapa K, Neupert W, Mokranjac D. Active remodelling of the TIM23 complex during translocation of preproteins into mitochondria. EMBO J. 2008;27:1469-80 pubmed publisher
    ..Our data demonstrate that the TIM23 complex acts as a single structural and functional entity that is actively remodelled to sort preproteins into different mitochondrial subcompartments. ..
  12. Mokranjac D, Popov Celeketic D, Hell K, Neupert W. Role of Tim21 in mitochondrial translocation contact sites. J Biol Chem. 2005;280:23437-40 pubmed
    ..We propose that Tim21 binds to the trans site of the TOM complex thus keeping the two translocases in close contact. ..
  13. Chacinska A, Rehling P, Guiard B, Frazier A, Schulze Specking A, Pfanner N, et al. Mitochondrial translocation contact sites: separation of dynamic and stabilizing elements in formation of a TOM-TIM-preprotein supercomplex. EMBO J. 2003;22:5370-81 pubmed
    ..b>Tim50, with its large IMS domain, is crucial for generation but not for stabilization of the supercomplex...
  14. Mokranjac D, Sichting M, Neupert W, Hell K. Tim14, a novel key component of the import motor of the TIM23 protein translocase of mitochondria. EMBO J. 2003;22:4945-56 pubmed
    ..We propose a model in which Tim14 is required for the activation of mtHsp70 and enables this chaperone to act in a rapid and regulated manner in the Tim44-mediated trapping of unfolded preproteins entering the matrix. ..
  15. Shiota T, Mabuchi H, Tanaka Yamano S, Yamano K, Endo T. In vivo protein-interaction mapping of a mitochondrial translocator protein Tom22 at work. Proc Natl Acad Sci U S A. 2011;108:15179-83 pubmed publisher
    ..of the outer membrane translocator TOM40 complex, with other translocator subunits such as Tom20, Tom40, and Tim50 and with substrate precursor proteins at a spatial resolution of the amino acid residue by in vivo and in ..
  16. 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...
  17. 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. ..
  18. Schulz C, Lytovchenko O, Melin J, Chacinska A, Guiard B, Neumann P, et al. Tim50's presequence receptor domain is essential for signal driven transport across the TIM23 complex. J Cell Biol. 2011;195:643-56 pubmed publisher
    ..on mitochondrial proteins were mapped mass spectrometrically, thereby defining a presequence-binding domain of Tim50, a core subunit of the TIM23 complex that is essential for mitochondrial protein import...
  19. Gebert M, Schrempp S, Mehnert C, Heißwolf A, Oeljeklaus S, Ieva R, et al. Mgr2 promotes coupling of the mitochondrial presequence translocase to partner complexes. J Cell Biol. 2012;197:595-604 pubmed publisher
    ..We conclude that Mgr2 is a coupling factor of the presequence translocase crucial for cell growth at elevated temperature and for efficient protein import. ..
  20. Matta S, Pareek G, Bankapalli K, Oblesha A, D Silva P. Role of Tim17 Transmembrane Regions in Regulating the Architecture of Presequence Translocase and Mitochondrial DNA Stability. Mol Cell Biol. 2017;37: pubmed publisher
    ..We conclude that the integrity of Tim17 transmembrane regions is critical for mitochondrial function and protein turnover. ..
  21. Demishtein Zohary K, Marom M, Neupert W, Mokranjac D, Azem A. GxxxG motifs hold the TIM23 complex together. FEBS J. 2015;282:2178-86 pubmed publisher
    ..We conclude that the GxxxG motifs found in the first and second transmembrane segments of Tim23 are necessary for the structural integrity of the TIM23 complex. ..
  22. 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...
  23. Demishtein Zohary K, Gunsel U, Marom M, Banerjee R, Neupert W, Azem A, et al. Role of Tim17 in coupling the import motor to the translocation channel of the mitochondrial presequence translocase. elife. 2017;6: pubmed publisher
  24. Bareth B, Nikolov M, Lorenzi I, Hildenbeutel M, Mick D, Helbig C, et al. Oms1 associates with cytochrome c oxidase assembly intermediates to stabilize newly synthesized Cox1. Mol Biol Cell. 2016;27:1570-80 pubmed publisher
    ..Our analyses show that Oms1 participates in cytochrome c oxidase assembly by stabilizing newly synthesized Cox1. ..
  25. Schulz C, Rehling P. Remodelling of the active presequence translocase drives motor-dependent mitochondrial protein translocation. Nat Commun. 2014;5:4349 pubmed publisher
    ..Thus, a replenishment cycle of co-chaperones at the TIM23 complex is an integral part of Hsp70's ATPase cycle at the channel exit site and essential to maintain motor-driven mitochondrial protein import. ..
  26. Rahman B, Kawano S, Yunoki Esaki K, Anzai T, Endo T. NMR analyses on the interactions of the yeast Tim50 C-terminal region with the presequence and Tim50 core domain. FEBS Lett. 2014;588:678-84 pubmed publisher
    ..targeting signal in the presequence of mitochondrial precursor proteins is recognized by Tom20 and subsequently by Tim50 in mitochondria...
  27. 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 ..
  28. Lytovchenko O, Melin J, Schulz C, Kilisch M, Hutu D, Rehling P. Signal recognition initiates reorganization of the presequence translocase during protein import. EMBO J. 2013;32:886-98 pubmed publisher
    ..Our analyses revealed that the presequence receptor Tim50 interacts with Tim21 in a signal-sensitive manner in a process that involves the IMS-domain of the Tim23 channel...
  29. Tamura Y, Endo T, Iijima M, Sesaki H. Ups1p and Ups2p antagonistically regulate cardiolipin metabolism in mitochondria. J Cell Biol. 2009;185:1029-45 pubmed publisher
    ..Furthermore, we observed synthetic growth defects in ups mutants in combination with loss of Pam17p, which controls the integrity of PAM. Our findings provide a novel molecular mechanism for the regulation of cardiolipin metabolism. ..
  30. Pareek G, Krishnamoorthy V, D Silva P. Molecular insights revealing interaction of Tim23 and channel subunits of presequence translocase. Mol Cell Biol. 2013;33:4641-59 pubmed publisher
    ..Our model conceptually explains the cooperative function between Tam41 and Pam17 subunits, while the antagonistic activity of Tim21 predominantly determines the bound and free forms of the PAM subcomplex during import. ..