TIM17

Summary

Gene Symbol: TIM17
Description: protein transporter TIM17
Alias: MIM17, MPI2, SMS1, protein transporter TIM17
Species: Saccharomyces cerevisiae S288c
Products:     TIM17

Top Publications

  1. Chacinska A, van der Laan M, Mehnert C, Guiard B, Mick D, Hutu D, et al. Distinct forms of mitochondrial TOM-TIM supercomplexes define signal-dependent states of preprotein sorting. Mol Cell Biol. 2010;30:307-18 pubmed publisher
    ..Depending on the signals of the preproteins, switches between the different forms of supercomplex and TIM23 are required for the completion of preprotein import. ..
  2. 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. ..
  3. Ryan K, Menold M, Garrett S, Jensen R. SMS1, a high-copy suppressor of the yeast mas6 mutant, encodes an essential inner membrane protein required for mitochondrial protein import. Mol Biol Cell. 1994;5:529-38 pubmed
    ..To identify new inner membrane import components, we isolated a high-copy suppressor (SMS1) of the mas6-1 mutant. SMS1 encodes a 16.5-kDa protein that contains several potential membrane-spanning domains...
  4. Wiedemann N, van der Laan M, Hutu D, Rehling P, Pfanner N. Sorting switch of mitochondrial presequence translocase involves coupling of motor module to respiratory chain. J Cell Biol. 2007;179:1115-22 pubmed
    ..The motor does not assemble en bloc with the translocase but apparently in a step-wise manner with the Pam16/18 module before the Hsp70 core. ..
  5. Martinez Caballero S, Grigoriev S, Herrmann J, Campo M, Kinnally K. Tim17p regulates the twin pore structure and voltage gating of the mitochondrial protein import complex TIM23. J Biol Chem. 2007;282:3584-93 pubmed
    ..These results suggest that although Tim23p is the main structural unit of the pore Tim17p is required for twin pore structure and provides the voltage gate for the TIM23 channel. ..
  6. 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. ..
  7. 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. ..
  8. 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. ..
  9. 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. ..

More Information

Publications56

  1. 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. ..
  2. Kozany C, Mokranjac D, Sichting M, Neupert W, Hell K. The J domain-related cochaperone Tim16 is a constituent of the mitochondrial TIM23 preprotein translocase. Nat Struct Mol Biol. 2004;11:234-41 pubmed
    ..In conclusion, Tim16 is a constituent of the TIM23 preprotein translocase, where it exerts crucial functions in the import motor. ..
  3. 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
  4. 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
    ..A translocation intermediate accumulated at the TOM complex is crosslinked to Tim50. We suggest that Tim50, in cooperation with Tim23, facilitates transfer of the translocating protein from the TOM complex to the TIM23 complex ..
  5. Mokranjac D, Berg A, Adam A, Neupert W, Hell K. Association of the Tim14.Tim16 subcomplex with the TIM23 translocase is crucial for function of the mitochondrial protein import motor. J Biol Chem. 2007;282:18037-45 pubmed
    ..Deletion of hydrophobic segments in both, Tim16 and Tim14, is lethal. We conclude that import into the matrix space of mitochondria requires association of the co-chaperones Tim16 and Tim14 with the TIM23 preprotein translocase. ..
  6. Dekker P, Martin F, Maarse A, Bömer U, Muller H, Guiard B, et al. The Tim core complex defines the number of mitochondrial translocation contact sites and can hold arrested preproteins in the absence of matrix Hsp70-Tim44. EMBO J. 1997;16:5408-19 pubmed
    ..By blue native electrophoresis, we identify an approximately 90K complex with assembled Tim23 and Tim17 as the core of the inner membrane import site for presequence-containing preproteins...
  7. 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. ..
  8. 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
  9. 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. ..
  10. 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
    ..A protruding ?-hairpin of Tim50 is crucial for interaction with Tim23, providing a molecular basis for the cooperation of Tim50 and Tim23 in preprotein translocation to the protein-conducting channel of the mitochondrial inner membrane. ..
  11. Popov Celeketic D, Waegemann K, Mapa K, Neupert W, Mokranjac D. Role of the import motor in insertion of transmembrane segments by the mitochondrial TIM23 complex. EMBO Rep. 2011;12:542-8 pubmed publisher
    ..Furthermore, our results suggest a role for the import motor in lateral insertion. Thus, the import motor is involved in ATP-dependent translocation and ATP-independent lateral insertion. ..
  12. 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. ..
  13. Berthold J, Bauer M, Schneider H, Klaus C, Dietmeier K, Neupert W, et al. The MIM complex mediates preprotein translocation across the mitochondrial inner membrane and couples it to the mt-Hsp70/ATP driving system. Cell. 1995;81:1085-93 pubmed
    ..Two known components, MIM23 and MIM17, and two novel components, MIM33 and MIM14, were found as constituents of this complex...
  14. 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
    ..Protein translocation into the matrix requires a switch to a Tim21-free, PAM bound presequence translocase. Tim17 is crucial for the switch by performing two separable functions: promotion of inner membrane insertion and binding ..
  15. Bömer U, Meijer M, Maarse A, Hönlinger A, Dekker P, Pfanner N, et al. Multiple interactions of components mediating preprotein translocation across the inner mitochondrial membrane. EMBO J. 1997;16:2205-16 pubmed
    The protein transport machinery of the inner mitochondrial membrane contains three essential Tim proteins. Tim17 and Tim23 are thought to build a preprotein translocation channel, while Tim44 transiently interacts with the matrix heat ..
  16. 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
    ..Thus, Tim50 functions as a dynamic factor and the IMS domain of Tom22 represents a stabilizing element in formation of a productive translocation contact site supercomplex. ..
  17. Blom J, Dekker P, Meijer M. Functional and physical interactions of components of the yeast mitochondrial inner-membrane import machinery (MIM). Eur J Biochem. 1995;232:309-14 pubmed
    ..other putative components of this protein-translocation system are the integral inner-membrane proteins, Mim23 and Mim17. Here, we present genetic evidence for functional co-operation of all three proteins...
  18. 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
    Import of proteins across the inner mitochondrial membrane through the Tim23:Tim17 translocase requires the function of an essential import motor having mitochondrial 70-kDa heat-shock protein (mtHsp70) at its core...
  19. Takeuchi J, Okada M, Toh e A, Kikuchi Y. The SMS1 gene encoding a serine-rich transmembrane protein suppresses the temperature sensitivity of the htr1 disruptant in Saccharomyces cerevisiae. Biochim Biophys Acta. 1995;1260:94-6 pubmed
    A new gene (SMS1; serine-rich multi-copy suppressor) of Saccharomyces cerevisiae was isolated by the ability to suppress the temperature sensitivity of the htr1 disruptant (Kikuchi et al. (1994) Mol. Gen...
  20. Ryan K, Leung R, Jensen R. Characterization of the mitochondrial inner membrane translocase complex: the Tim23p hydrophobic domain interacts with Tim17p but not with other Tim23p molecules. Mol Cell Biol. 1998;18:178-87 pubmed
    ..In contrast, Tim23Cp cannot be coimmunoprecipitated with Tim23p, raising the possibility that the hydrophobic domain of Tim23p does not interact with other Tim23 molecules. ..
  21. 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 ??- and Pam17-dependent import step identified in this study is positioned between the two known energy-dependent steps: ??-driven presequence translocation and adenosine triphosphate-driven import motor activity. ..
  22. 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
    We have analysed the structural organization of the TIM17.23 complex, the preprotein translocase of the mitochondrial inner membrane specific for protein targeting to the matrix...
  23. Sirrenberg C, Endres M, FOLSCH H, Stuart R, Neupert W, Brunner M. Carrier protein import into mitochondria mediated by the intermembrane proteins Tim10/Mrs11 and Tim12/Mrs5. Nature. 1998;391:912-5 pubmed
    ..targeting signals are translocated into the matrix by the integral inner membrane proteins Tim23 and Tim17 in cooperation with Tim44 and mitochondrial Hsp70...
  24. Iacovino M, Granycome C, Sembongi H, Bokori Brown M, Butow R, Holt I, et al. The conserved translocase Tim17 prevents mitochondrial DNA loss. Hum Mol Genet. 2009;18:65-74 pubmed publisher
    ..We have identified OXA1 and TIM17 as novel multicopy suppressors of mtDNA instability in ilv5 cells...
  25. 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. ..
  26. Bömer U, Meijer M, Guiard B, Dietmeier K, Pfanner N, Rassow J. The sorting route of cytochrome b2 branches from the general mitochondrial import pathway at the preprotein translocase of the inner membrane. J Biol Chem. 1997;272:30439-46 pubmed
    ..We suggest that the sorting signal of cytochrome b2 is recognized within the inner membrane in close vicinity to Tim23. ..
  27. 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. ..
  28. 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
    ..The translocon is composed of the two integral membrane proteins Tim23 and Tim17, each containing four membrane-spanning segments...
  29. Schilke B, Hayashi M, Craig E. Genetic analysis of complex interactions among components of the mitochondrial import motor and translocon in Saccharomyces cerevisiae. Genetics. 2012;190:1341-53 pubmed publisher
    ..of genetic interactions and enhanced Pam17 translocon association was observed in the absence of the C terminus of Tim17, a core component of the translocon...
  30. 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. ..
  31. 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. ..
  32. 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
    Proteins destined for the mitochondrial matrix are targeted to the inner membrane Tim17/23 translocon by their presequences. Inward movement is driven by the matrix-localized, Hsp70-based motor...
  33. Sichting M, Mokranjac D, Azem A, Neupert W, Hell K. Maintenance of structure and function of mitochondrial Hsp70 chaperones requires the chaperone Hep1. EMBO J. 2005;24:1046-56 pubmed
    ..This process is efficiently counteracted by Hep1. We conclude that Hep1 acts as a chaperone that is necessary and sufficient to prevent self-aggregation and to thereby maintain the function of the mitochondrial Hsp70 chaperones. ..
  34. Jia L, Kaur J, Stuart R. Mapping of the Saccharomyces cerevisiae Oxa1-mitochondrial ribosome interface and identification of MrpL40, a ribosomal protein in close proximity to Oxa1 and critical for oxidative phosphorylation complex assembly. Eukaryot Cell. 2009;8:1792-802 pubmed publisher
  35. Schuler M, Di Bartolomeo F, Mårtensson C, Daum G, Becker T. Phosphatidylcholine Affects Inner Membrane Protein Translocases of Mitochondria. J Biol Chem. 2016;291:18718-29 pubmed publisher
    ..We conclude that reduced PC levels differentially affect the TIM22 and TIM23 complexes in mitochondrial protein transport. ..
  36. SCHULKE N, Sepuri N, Gordon D, Saxena S, Dancis A, Pain D. A multisubunit complex of outer and inner mitochondrial membrane protein translocases stabilized in vivo by translocation intermediates. J Biol Chem. 1999;274:22847-54 pubmed
    ..all Tom and Tim components known to be essential for import of matrix-targeted proteins, namely Tom40, Tom22, Tim17, Tim23, Tim44, and matrix-localized Hsp70...
  37. Kerscher O, Sepuri N, Jensen R. Tim18p is a new component of the Tim54p-Tim22p translocon in the mitochondrial inner membrane. Mol Biol Cell. 2000;11:103-16 pubmed
    ..We propose that Tim18p is a new component of the Tim54p-Tim22p machinery that facilitates insertion of polytopic proteins into the mitochondrial inner membrane. ..
  38. Ramesh A, Peleh V, Martinez Caballero S, Wollweber F, Sommer F, van der Laan M, et al. A disulfide bond in the TIM23 complex is crucial for voltage gating and mitochondrial protein import. J Cell Biol. 2016;214:417-31 pubmed publisher
    b>Tim17 is a central, membrane-embedded subunit of the mitochondrial protein import machinery...
  39. 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
    ..b>Tim17 is an essential, membrane-embedded subunit of the translocase; however, its function is only poorly understood...
  40. 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. ..
  41. Häcker I, Sander B, Golas M, Wolf E, Karagöz E, Kastner B, et al. Localization of Prp8, Brr2, Snu114 and U4/U6 proteins in the yeast tri-snRNP by electron microscopy. Nat Struct Mol Biol. 2008;15:1206-12 pubmed publisher
    ..The head and arm adopt variable relative positions. This molecular organization and dynamics suggest possible scenarios for structural events during catalytic activation. ..
  42. 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
    ..Tim23 forms the core of the voltage-gated import channel, while Tim17 is presumed to maintain the stoichiometry of the translocase...
  43. Kerscher O, Holder J, Srinivasan M, Leung R, Jensen R. The Tim54p-Tim22p complex mediates insertion of proteins into the mitochondrial inner membrane. J Cell Biol. 1997;139:1663-75 pubmed
    ..First, multiple copies of the TIM22 gene, but not TIM23 or TIM17, suppress the growth defect of a tim54-1 temperature-sensitive mutant...
  44. 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
    ..that the TM1 and TM2 from each dimer are involved in the formation of the central translocation pore, aided by Tim17. Furthermore, TM2 is also involved in the recruitment of Tim21 and the presequence-associated motor (PAM) ..
  45. 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. ..
  46. Meier S, Neupert W, Herrmann J. Conserved N-terminal negative charges in the Tim17 subunit of the TIM23 translocase play a critical role in the import of preproteins into mitochondria. J Biol Chem. 2005;280:7777-85 pubmed
    ..This translocase consists of the two phylogenetically related membrane-embedded subunits Tim17 and Tim23 to which four largely hydrophilic subunits, Tim50, Tim44, Tim16, and Tim14, are attached...
  47. Milisav I, Moro F, Neupert W, Brunner M. Modular structure of the TIM23 preprotein translocase of mitochondria. J Biol Chem. 2001;276:25856-61 pubmed
    ..It is composed of the integral membrane proteins Tim17 and Tim23 and the peripheral membrane protein Tim44, which recruits mitochondrial Hsp70 to the sites of protein ..