TOM40

Summary

Gene Symbol: TOM40
Description: Tom40p
Alias: ISP42, MOM38, Tom40p
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Kutik S, Stojanovski D, Becker L, Becker T, Meinecke M, Krüger V, et al. Dissecting membrane insertion of mitochondrial beta-barrel proteins. Cell. 2008;132:1011-24 pubmed publisher
    ..We propose that a two-stage mechanism of signal-driven insertion into a membrane protein complex and subsequent integration into the lipid phase may represent a general mechanism for biogenesis of beta-barrel proteins. ..
  2. Becker T, Wenz L, Krüger V, Lehmann W, Müller J, Goroncy L, et al. The mitochondrial import protein Mim1 promotes biogenesis of multispanning outer membrane proteins. J Cell Biol. 2011;194:387-95 pubmed publisher
    ..We conclude that the Mim1 complex plays a central role in the import of ?-helical outer membrane proteins with multiple transmembrane segments. ..
  3. Thornton N, Stroud D, Milenkovic D, Guiard B, Pfanner N, Becker T. Two modular forms of the mitochondrial sorting and assembly machinery are involved in biogenesis of alpha-helical outer membrane proteins. J Mol Biol. 2010;396:540-9 pubmed publisher
    ..complex is required for the assembly of precursors of the TOM complex, including not only the beta-barrel protein Tom40 but also a subset of alpha-helical subunits...
  4. Rapaport D, Neupert W. Biogenesis of Tom40, core component of the TOM complex of mitochondria. J Cell Biol. 1999;146:321-31 pubmed
    b>Tom40 is an essential component of the preprotein translocase of the mitochondrial outer membrane (TOM complex) in which it constitutes the core element of the protein conducting pore. We have investigated the biogenesis of Tom40...
  5. Chan N, Lithgow T. The peripheral membrane subunits of the SAM complex function codependently in mitochondrial outer membrane biogenesis. Mol Biol Cell. 2008;19:126-36 pubmed
    ..Very different environments surround bacteria and mitochondria, and we discuss the role of Sam35 and Sam37 in terms of the problems peculiar to mitochondrial protein substrates. ..
  6. Habib S, Waizenegger T, Lech M, Neupert W, Rapaport D. Assembly of the TOB complex of mitochondria. J Biol Chem. 2005;280:6434-40 pubmed
    ..Next, it is transferred through the import channel formed by Tom40. Variants of the latter protein influenced the insertion of Tob55...
  7. Becker T, Guiard B, Thornton N, Zufall N, Stroud D, Wiedemann N, et al. Assembly of the mitochondrial protein import channel: role of Tom5 in two-stage interaction of Tom40 with the SAM complex. Mol Biol Cell. 2010;21:3106-13 pubmed publisher
    The preprotein translocase of the outer mitochondrial membrane (TOM) consists of a central ?-barrel channel, Tom40, and six proteins with ?-helical transmembrane segments...
  8. Stroud D, Becker T, Qiu J, Stojanovski D, Pfannschmidt S, Wirth C, et al. Biogenesis of mitochondrial ?-barrel proteins: the POTRA domain is involved in precursor release from the SAM complex. Mol Biol Cell. 2011;22:2823-33 pubmed publisher
    ..These results indicate the POTRA domain of Sam50 is not essential for recognition of ?-barrel precursors but functions in a subsequent step to promote the release of precursor proteins from the SAM complex. ..
  9. Stojanovski D, Milenkovic D, Müller J, Gabriel K, Schulze Specking A, Baker M, et al. Mitochondrial protein import: precursor oxidation in a ternary complex with disulfide carrier and sulfhydryl oxidase. J Cell Biol. 2008;183:195-202 pubmed publisher

More Information

Publications53

  1. 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. ..
  2. Krimmer T, Rapaport D, Ryan M, Meisinger C, Kassenbrock C, Blachly Dyson E, et al. Biogenesis of porin of the outer mitochondrial membrane involves an import pathway via receptors and the general import pore of the TOM complex. J Cell Biol. 2001;152:289-300 pubmed
    ..The characterization of two new mutant alleles of the essential pore protein Tom40 demonstrates that the import of porin also requires a functional Tom40...
  3. Yamano K, Tanaka Yamano S, Endo T. Tom7 regulates Mdm10-mediated assembly of the mitochondrial import channel protein Tom40. J Biol Chem. 2010;285:41222-31 pubmed publisher
    barrel membrane proteins in the mitochondrial outer membrane use the TOM40 complex to enter mitochondria and then the TOB/SAM complex to be assembled into the outer membrane...
  4. Dietmeier K, Hönlinger A, Bömer U, Dekker P, Eckerskorn C, Lottspeich F, et al. Tom5 functionally links mitochondrial preprotein receptors to the general import pore. Nature. 1997;388:195-200 pubmed
    ..b>Tom40 is an essential constituent of the GIP, whereas Tom6 and Tom7 modulate the assembly and dissociation of the Tom ..
  5. Wrobel L, Trojanowska A, Sztolsztener M, Chacinska A. Mitochondrial protein import: Mia40 facilitates Tim22 translocation into the inner membrane of mitochondria. Mol Biol Cell. 2013;24:543-54 pubmed publisher
    ..We propose that Mia40 not only is responsible for disulfide bond formation, but also assists the Tim22 protein in its integration into the inner membrane of mitochondria. ..
  6. Becker T, Pfannschmidt S, Guiard B, Stojanovski D, Milenkovic D, Kutik S, et al. Biogenesis of the mitochondrial TOM complex: Mim1 promotes insertion and assembly of signal-anchored receptors. J Biol Chem. 2008;283:120-7 pubmed
    ..The channel-forming beta-barrel protein Tom40 is targeted to mitochondria via Tom receptors and inserted into the outer membrane by the sorting and assembly ..
  7. Court D, Nargang F, Steiner H, Hodges R, Neupert W, Lill R. Role of the intermembrane-space domain of the preprotein receptor Tom22 in protein import into mitochondria. Mol Cell Biol. 1996;16:4035-42 pubmed
    ..Rather, the IMS domain of Tom22 appears to slightly enhance the efficiency of the transfer of these preproteins to the import machinery of the inner membrane. ..
  8. 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. ..
  9. Zerbes R, Bohnert M, Stroud D, von der Malsburg K, Kram A, Oeljeklaus S, et al. Role of MINOS in mitochondrial membrane architecture: cristae morphology and outer membrane interactions differentially depend on mitofilin domains. J Mol Biol. 2012;422:183-91 pubmed publisher
  10. 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. ..
  11. Dekker P, Ryan M, Brix J, Muller H, Hönlinger A, Pfanner N. Preprotein translocase of the outer mitochondrial membrane: molecular dissection and assembly of the general import pore complex. Mol Cell Biol. 1998;18:6515-24 pubmed
    ..We have analyzed the molecular architecture of the Tom machinery. The receptor Tom22 stably associates with Tom40, the main component of the GIP, in a complex with a molecular weight of approximately 400,000 ( approximately 400K)..
  12. Hönlinger A, Bömer U, Alconada A, Eckerskorn C, Lottspeich F, Dietmeier K, et al. Tom7 modulates the dynamics of the mitochondrial outer membrane translocase and plays a pathway-related role in protein import. EMBO J. 1996;15:2125-37 pubmed
    ..A lack of Tom7 stabilized the interaction between the receptors Tom20 and Tom22 and the import pore component Tom40. This indicated that Tom7 exerts a destabilizing effect on part of the outer membrane translocase, whereas Tom6 ..
  13. Model K, Meisinger C, Prinz T, Wiedemann N, Truscott K, Pfanner N, et al. Multistep assembly of the protein import channel of the mitochondrial outer membrane. Nat Struct Biol. 2001;8:361-70 pubmed
    ..The precursor of the channel-lining Tom40 is first targeted to the membrane via the receptor proteins Tom20 and Tom22; it then assembles with Tom5 to form ..
  14. Becker L, Bannwarth M, Meisinger C, Hill K, Model K, Krimmer T, et al. Preprotein translocase of the outer mitochondrial membrane: reconstituted Tom40 forms a characteristic TOM pore. J Mol Biol. 2005;353:1011-20 pubmed publisher
    b>Tom40 is the central pore-forming component of the translocase of the outer mitochondrial membrane (TOM complex)...
  15. Hill K, Model K, Ryan M, Dietmeier K, Martin F, Wagner R, et al. Tom40 forms the hydrophilic channel of the mitochondrial import pore for preproteins [see comment]. Nature. 1998;395:516-21 pubmed
    ..Here we describe the expression and functional reconstitution of Tom40, an integral membrane protein with mainly beta-sheet structure...
  16. Yamano K, Tanaka Yamano S, Endo T. Mdm10 as a dynamic constituent of the TOB/SAM complex directs coordinated assembly of Tom40. EMBO Rep. 2010;11:187-93 pubmed publisher
    The mitochondrial outer membrane contains two protein translocators: the TOM40 and TOB/SAM complexes...
  17. van Wilpe S, Ryan M, Hill K, Maarse A, Meisinger C, Brix J, et al. Tom22 is a multifunctional organizer of the mitochondrial preprotein translocase. Nature. 1999;401:485-9 pubmed
    ..both its cytosolic domain and its intermembrane space domain and is stably associated with the channel protein Tom40 (refs 11-13)...
  18. 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. ..
  19. Schmidt O, Harbauer A, Rao S, Eyrich B, Zahedi R, Stojanovski D, et al. Regulation of mitochondrial protein import by cytosolic kinases. Cell. 2011;144:227-39 pubmed publisher
    ..We conclude that cytosolic kinases exert stimulatory and inhibitory effects on biogenesis and function of the TOM complex and thus regulate protein import into mitochondria. ..
  20. Kuzmenko A, Tankov S, English B, Tarassov I, Tenson T, Kamenski P, et al. Single molecule tracking fluorescence microscopy in mitochondria reveals highly dynamic but confined movement of Tom40. Sci Rep. 2011;1:195 pubmed publisher
    b>Tom40 is an integral protein of the mitochondrial outer membrane, which as the central component of the Translocase of the Outer Membrane (TOM) complex forms a channel for protein import...
  21. 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
    ..Here we analyze the interactions of Tom22, a multifunctional subunit of the outer membrane translocator TOM40 complex, with other translocator subunits such as Tom20, Tom40, and Tim50 and with substrate precursor proteins at ..
  22. Stan T, Brix J, Schneider Mergener J, Pfanner N, Neupert W, Rapaport D. Mitochondrial protein import: recognition of internal import signals of BCS1 by the TOM complex. Mol Cell Biol. 2003;23:2239-50 pubmed
  23. Bohnert M, Wenz L, Zerbes R, Horvath S, Stroud D, von der Malsburg K, et al. Role of mitochondrial inner membrane organizing system in protein biogenesis of the mitochondrial outer membrane. Mol Biol Cell. 2012;23:3948-56 pubmed publisher
    ..We conclude that MINOS interacts with TOM and SAM independently and that the core subunit mitofilin is involved in biogenesis of outer membrane ?-barrel proteins. ..
  24. Reinhold R, Krüger V, Meinecke M, Schulz C, Schmidt B, Grunau S, et al. The channel-forming Sym1 protein is transported by the TIM23 complex in a presequence-independent manner. Mol Cell Biol. 2012;32:5009-21 pubmed publisher
  25. Herndon J, Claypool S, Koehler C. The Taz1p transacylase is imported and sorted into the outer mitochondrial membrane via a membrane anchor domain. Eukaryot Cell. 2013;12:1600-8 pubmed publisher
    ..These studies suggest that altering the mitochondrial import pathway of Taz1p may be important in understanding the molecular basis of Barth syndrome. ..
  26. Gornicka A, Bragoszewski P, Chrościcki P, Wenz L, Schulz C, Rehling P, et al. A discrete pathway for the transfer of intermembrane space proteins across the outer membrane of mitochondria. Mol Biol Cell. 2014;25:3999-4009 pubmed publisher
    ..Here we demonstrate that this alternative pathway involves the protein channel formed by Tom40. We sought a translocation intermediate by expressing tagged versions of MIA-dependent proteins in vivo...
  27. Kassenbrock C, Gao G, Groom K, Sulo P, Douglas M, Martin N. RPM2, independently of its mitochondrial RNase P function, suppresses an ISP42 mutant defective in mitochondrial import and is essential for normal growth. Mol Cell Biol. 1995;15:4763-70 pubmed
    RPM2 is identified here as a high-copy suppressor of isp42-3, a temperature-sensitive mutant allele of the mitochondrial protein import channel component, Isp42p...
  28. Stribinskis V, Heyman H, Ellis S, Steffen M, Martin N. Rpm2p, a component of yeast mitochondrial RNase P, acts as a transcriptional activator in the nucleus. Mol Cell Biol. 2005;25:6546-58 pubmed
    ..Rpm2p also increases the level of Tom40p, as well as Hsp60p, but not Atp2p, suggesting that some, but not all, nucleus-encoded mitochondrial components are ..
  29. 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. ..
  30. Amutha B, Pain D. Nucleoside diphosphate kinase of Saccharomyces cerevisiae, Ynk1p: localization to the mitochondrial intermembrane space. Biochem J. 2003;370:805-15 pubmed
    ..by our observations that interaction with a 40 kDa protein of the translocase of outer mitochondrial membrane (Tom40p), occurs preferentially with unfolded, unphosphorylated forms of Ynk1p...
  31. Gaikwad A, Cumsky M. The use of chemical cross-linking to identify proteins that interact with a mitochondrial presequence. J Biol Chem. 1994;269:6437-43 pubmed
    ..Two of the cross-linked species corresponded to the outer membrane proteins, Mas70p and ISP42. Significantly, both of these proteins have previously been shown to play critical roles in mitochondrial protein ..
  32. 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
    ..that contains 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...
  33. Model K, Meisinger C, Kuhlbrandt W. Cryo-electron microscopy structure of a yeast mitochondrial preprotein translocase. J Mol Biol. 2008;383:1049-57 pubmed publisher
    ..Based on our three-dimensional map, we propose a model of transient interactions and functional dynamics of the TOM assembly. ..
  34. Lin Z, Dong M, Zhang Y, Lee E, Lin H. Cbr1 is a Dph3 reductase required for the tRNA wobble uridine modification. Nat Chem Biol. 2016;12:995-997 pubmed publisher
    ..The NADH- and Cbr1-dependent reduction of Dph3 may provide a regulatory linkage between cellular metabolic state and protein translation. ..
  35. Moczko M, Dietmeier K, Sollner T, Segui B, Steger H, Neupert W, et al. Identification of the mitochondrial receptor complex in Saccharomyces cerevisiae. FEBS Lett. 1992;310:265-8 pubmed
    ..We isolated a complex out of S. cerevisiae mitochondria consisting of MOM38/ISP42, the receptor MOM72, and five new yeast proteins, the putative equivalents of N...
  36. Kassenbrock C, Cao W, Douglas M. Genetic and biochemical characterization of ISP6, a small mitochondrial outer membrane protein associated with the protein translocation complex. EMBO J. 1993;12:3023-34 pubmed
    ..PCR mutagenesis to generate temperature-sensitive mutants in the outer membrane translocation pore component ISP42. A high copy number suppressor of temperature-sensitive isp42 has been isolated and sequenced...
  37. Gordon D, Wang J, Amutha B, Pain D. Self-association and precursor protein binding of Saccharomyces cerevisiae Tom40p, the core component of the protein translocation channel of the mitochondrial outer membrane. Biochem J. 2001;356:207-15 pubmed
    ..Tom) is a multi-subunit complex containing receptors and a general import channel, of which the core component is Tom40p. Nuclear-encoded mitochondrial precursor proteins are first recognized by surface receptors and then pass through ..
  38. Stribinskis V, Gao G, Ellis S, Martin N. Rpm2, the protein subunit of mitochondrial RNase P in Saccharomyces cerevisiae, also has a role in the translation of mitochondrially encoded subunits of cytochrome c oxidase. Genetics. 2001;158:573-85 pubmed
    ..Moreover, there is a synthetic lethal interaction between the disruption of this novel respiratory function and the loss of wild-type mtDNA. This synthetic interaction explains why a complete deletion of RPM2 is lethal. ..
  39. 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
    ..Thus, Tim50 is crucial for guiding the precursors of matrix proteins to their insertion site in the inner membrane. ..
  40. Horvath S, Böttinger L, Vögtle F, Wiedemann N, Meisinger C, Becker T, et al. Processing and topology of the yeast mitochondrial phosphatidylserine decarboxylase 1. J Biol Chem. 2012;287:36744-55 pubmed publisher
    ..In summary, membrane integration of Psd1 is crucial for its functionality and for maintenance of mitochondrial lipid homeostasis. ..
  41. Melin J, Schulz C, Wrobel L, Bernhard O, Chacinska A, Jahn O, et al. Presequence recognition by the tom40 channel contributes to precursor translocation into the mitochondrial matrix. Mol Cell Biol. 2014;34:3473-85 pubmed publisher
    ..However, after the presequence enters the protein-conducting Tom40 channel, the recognition events that occur at the trans side leading up to the engagement of the presequence with ..
  42. Model K, Prinz T, Ruiz T, Radermacher M, Krimmer T, Kuhlbrandt W, et al. Protein translocase of the outer mitochondrial membrane: role of import receptors in the structural organization of the TOM complex. J Mol Biol. 2002;316:657-66 pubmed
    ..of the outer membrane (TOM) consists of three receptor proteins, Tom20, Tom22 and Tom70, the channel protein Tom40, and several small Tom proteins...
  43. Wenz L, Ellenrieder L, Qiu J, Bohnert M, Zufall N, van der Laan M, et al. Sam37 is crucial for formation of the mitochondrial TOM-SAM supercomplex, thereby promoting β-barrel biogenesis. J Cell Biol. 2015;210:1047-54 pubmed publisher
    ..Sam37 thus promotes efficient transfer of β-barrel precursors to the SAM complex. We conclude that Sam37 functions as a coupling factor of the translocase supercomplex of the mitochondrial outer membrane. ..
  44. 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
    ..most of their resident proteins from the cytosol, and the import receptor Tom20 of the outer-membrane translocator TOM40 complex plays an essential role in specificity of mitochondrial protein import...