PAM18

Summary

Gene Symbol: PAM18
Description: Pam18p
Alias: TIM14, Pam18p
Species: Saccharomyces cerevisiae S288c
Products:     PAM18

Top Publications

  1. Elsner S, Simian D, Iosefson O, Marom M, Azem A. The mitochondrial protein translocation motor: structural conservation between the human and yeast Tim14/Pam18-Tim16/Pam16 co-chaperones. Int J Mol Sci. 2009;10:2041-53 pubmed publisher
    ..Of particular interest for us is the human Tim14/Pam18-Tim16/Pam16 complex...
  2. 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
    ..complex, depletion of Tam41 led to a decreased molecular size of the TIM23 complex and partial aggregation of Pam18 and -16...
  3. 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
    The TIM23 translocase mediates the deltaPsi- and ATP-dependent import of proteins into mitochondria. We identified Tim14 as a novel component of the TIM23 translocase...
  4. 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
    ..Magmas forms a stable subcomplex with J-protein Pam18 or DnaJC19 through its C-terminal region and is tethered to TIM23 complex of yeast and humans...
  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. 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. ..
  7. Mokranjac D, Sichting M, Popov Celeketic D, Berg A, Hell K, Neupert W. The import motor of the yeast mitochondrial TIM23 preprotein translocase contains two different J proteins, Tim14 and Mdj2. J Biol Chem. 2005;280:31608-14 pubmed
    ..It recruits mtHsp70, which binds the incoming preproteins. The J protein Tim14 stimulates the ATPase activity of mtHsp70 and thereby enables efficient binding of mtHsp70 to preproteins...
  8. Slutsky Leiderman O, Marom M, Iosefson O, Levy R, Maoz S, Azem A. The interplay between components of the mitochondrial protein translocation motor studied using purified components. J Biol Chem. 2007;282:33935-42 pubmed
    ..Tim44; 3) the nucleotide exchange factor Mge1; and 4) a J-domain-containing complex of co-chaperones, Tim14/Pam18-Tim16/Pam16...
  9. Mokranjac D, Bourenkov G, Hell K, Neupert W, Groll M. Structure and function of Tim14 and Tim16, the J and J-like components of the mitochondrial protein import motor. EMBO J. 2006;25:4675-85 pubmed
    ..essential step of this process is the stimulation of the ATPase activity of mtHsp70 performed by the J cochaperone Tim14. Tim14 forms a complex with the J-like protein Tim16...

More Information

Publications39

  1. 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
    b>Tim14 and Tim16 are essential components of the import motor of the mitochondrial TIM23 preprotein translocase. Tim14 contains a J domain in the matrix space that is anchored in the inner membrane by a transmembrane segment...
  2. Truscott K, Voos W, Frazier A, Lind M, Li Y, Geissler A, et al. A J-protein is an essential subunit of the presequence translocase-associated protein import motor of mitochondria. J Cell Biol. 2003;163:707-13 pubmed
    ..The novel J-protein (encoded by PAM18/YLR008c/TIM14) is required for the interaction of mtHsp70 with Tim44 and protein translocation into the matrix...
  3. 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
    ..This reaction is assisted by the cochaperones Tim14 and Mge1. We have identified a novel essential cochaperone, Tim16...
  4. 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
    ..The heterodimer composed of Pam18, the J-protein partner of mtHsp70, and the related protein Pam16 is a critical component of this motor...
  5. 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
    ..are regulated by four membrane-associated cochaperones: the adaptor protein Tim44, the stimulatory J-complex Pam18/Pam16, and Pam17...
  6. D Silva P, Schilke B, Walter W, Craig E. Role of Pam16's degenerate J domain in protein import across the mitochondrial inner membrane. Proc Natl Acad Sci U S A. 2005;102:12419-24 pubmed
    ..The J protein partner of mtHsp70, Pam18, is an integral part of this motor, serving to stimulate the ATPase activity of mtHsp70...
  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
    ..exchange factor Mge1, Tim44 that directs mtHsp70 to the inner membrane, and the membrane-bound complex of Pam16-Pam18 that regulates the ATPase activity of mtHsp70. We have identified a sixth motor subunit...
  8. D Silva P, Schilke B, Walter W, Andrew A, Craig E. J protein cochaperone of the mitochondrial inner membrane required for protein import into the mitochondrial matrix. Proc Natl Acad Sci U S A. 2003;100:13839-44 pubmed
    ..However, a previously unstudied essential gene, PAM18, encodes an 18-kDa protein that contains a J domain and is localized to the mitochondrial inner membrane...
  9. 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. ..
  10. 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
  11. 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
    ..four essential subunits: the matrix heat shock protein 70 (mtHsp70) and its three cochaperones Mge1, Tim44 and Pam18. Here we report that the PAM contains a fifth essential subunit, Pam16 (encoded by Saccharomyces cerevisiae ..
  12. 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
    ..crucial for the switch by performing two separable functions: promotion of inner membrane insertion and binding of Pam18 to form the functional TIM-PAM complex...
  13. 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. ..
  14. 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
    ..As both Tim44 and Pam17 have been implicated as regulatory subunits of the motor, this positioning is conducive for responding to conformational changes in the translocon upon a translocating polypeptide entering the channel. ..
  15. 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
  16. 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. ..
  17. 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. ..
  18. 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. ..
  19. Goswami A, Samaddar M, Sinha D, Purushotham J, D Silva P. Enhanced J-protein interaction and compromised protein stability of mtHsp70 variants lead to mitochondrial dysfunction in Parkinson's disease. Hum Mol Genet. 2012;21:3317-32 pubmed publisher
    ..Taken together, our findings provide evidence in favor of direct involvement of mtHsp70 as a susceptibility factor in PD. ..
  20. 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
    ..Stimulation of Hsp70's ATPase activity by the translocon-associated J-protein Pam18 is critical for this process...
  21. Becker D, Krayl M, Strub A, Li Y, Mayer M, Voos W. Impaired interdomain communication in mitochondrial Hsp70 results in the loss of inward-directed translocation force. J Biol Chem. 2009;284:2934-46 pubmed publisher
    ..We conclude that even a partial disruption of the interdomain communication in the mtHsp70 chaperone results in an almost complete breakdown of its translocation-driving properties. ..
  22. 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
    ..Our data suggest a model in which the CTD serves primarily to anchor Tim44 to the translocon, whereas the NTD is a dynamic arm, interacting with multiple components to drive efficient translocation. ..
  23. 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
    ..Hsp70 is tethered to the translocon via interaction with Tim44. Pam18, the J-protein co-chaperone, and Pam16, a structurally related protein with which Pam18 forms a heterodimer, are ..
  24. Hayashi M, Schilke B, Marszalek J, Williams B, Craig E. Ancient gene duplication provided a key molecular step for anaerobic growth of Baker's yeast. Mol Biol Evol. 2011;28:2005-17 pubmed publisher
    ..In Saccharomyces cerevisiae, two paralogous J-proteins, Pam18 and Mdj2, can form the import motor...
  25. Schulz C, Rehling P. Remodelling of the active presequence translocase drives motor-dependent mitochondrial protein translocation. Nat Commun. 2014;5:4349 pubmed publisher
    ..translocase and find that regulatory subunits of the import motor, such as the ATPase-stimulating J-protein Pam18, are recruited into the translocation intermediate...
  26. 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. ..
  27. 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. ..
  28. 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. ..
  29. Böttinger L, Gornicka A, Czerwik T, Bragoszewski P, Loniewska Lwowska A, Schulze Specking A, et al. In vivo evidence for cooperation of Mia40 and Erv1 in the oxidation of mitochondrial proteins. Mol Biol Cell. 2012;23:3957-69 pubmed publisher
    ..Thus Mia40 in cooperation with Erv1 promotes the formation of two disulfide bonds in the substrate protein, ensuring the efficiency of oxidative folding in the intermembrane space of mitochondria. ..
  30. Sahi C, Kominek J, Ziegelhoffer T, Yu H, Baranowski M, Marszalek J, et al. Sequential duplications of an ancient member of the DnaJ-family expanded the functional chaperone network in the eukaryotic cytosol. Mol Biol Evol. 2013;30:985-98 pubmed publisher