Crossref journal-article
Rockefeller University Press
Journal of Cell Biology (291)
Abstract

Many mitochondrial proteins are synthesized with N-terminal presequences in the cytosol. The presequence translocase of the inner mitochondrial membrane (TIM23) translocates preproteins into and across the membrane and associates with the matrix-localized import motor. The TIM23 complex consists of three core components and Tim21, which interacts with the translocase of the outer membrane (TOM) and the respiratory chain. We have identified a new subunit of the TIM23 complex, the inner membrane protein Mgr2. Mitochondria lacking Mgr2 were deficient in the Tim21-containing sorting form of the TIM23 complex. Mgr2 was required for binding of Tim21 to TIM23CORE, revealing a binding chain of TIM23CORE-Mgr2/Tim21–respiratory chain. Mgr2-deficient yeast cells were defective in growth at elevated temperature, and the mitochondria were impaired in TOM-TIM23 coupling and the import of presequence-carrying preproteins. We conclude that Mgr2 is a coupling factor of the presequence translocase crucial for cell growth at elevated temperature and for efficient protein import.

Bibliography

Gebert, M., Schrempp, S. G., Mehnert, C. S., Heißwolf, A. K., Oeljeklaus, S., Ieva, R., Bohnert, M., von der Malsburg, K., Wiese, S., Kleinschroth, T., Hunte, C., Meyer, H. E., Haferkamp, I., Guiard, B., Warscheid, B., Pfanner, N., & van der Laan, M. (2012). Mgr2 promotes coupling of the mitochondrial presequence translocase to partner complexes. Journal of Cell Biology, 197(5), 595–604.

Authors 17
  1. Michael Gebert (first)
  2. Sandra G. Schrempp (additional)
  3. Carola S. Mehnert (additional)
  4. Anna K. Heißwolf (additional)
  5. Silke Oeljeklaus (additional)
  6. Raffaele Ieva (additional)
  7. Maria Bohnert (additional)
  8. Karina von der Malsburg (additional)
  9. Sebastian Wiese (additional)
  10. Thomas Kleinschroth (additional)
  11. Carola Hunte (additional)
  12. Helmut E. Meyer (additional)
  13. Ilka Haferkamp (additional)
  14. Bernard Guiard (additional)
  15. Bettina Warscheid (additional)
  16. Nikolaus Pfanner (additional)
  17. Martin van der Laan (additional)
References 68 Referenced 83
  1. 10.1016/S0092-8674(00)80691-1 / Cell. / Structural basis of presequence recognition by the mitochondrial protein import receptor Tom20 by Abe (2000)
  2. 10.1038/sj.embor.7400828 / EMBO Rep. / The Tim21 binding domain connects the preprotein translocases of both mitochondrial membranes by Albrecht (2006)
  3. 10.1016/j.jmb.2010.11.002 / J. Mol. Biol. / Biogenesis of mitochondria: Dual role of Tom7 in modulating assembly of the preprotein translocase of the outer membrane by Becker (2011)
  4. 10.1038/emboj.2011.169 / EMBO J. / Presequence-dependent folding ensures MrpL32 processing by the m-AAA protease in mitochondria by Bonn (2011)
  5. 10.1074/jbc.M412269200 / J. Biol. Chem. / The carboxyl-terminal third of the dicarboxylate carrier is crucial for productive association with the inner membrane twin-pore translocase by Brandner (2005)
  6. 10.1074/jbc.274.23.16522 / J. Biol. Chem. / Distribution of binding sequences for the mitochondrial import receptors Tom20, Tom22, and Tom70 in a presequence-carrying preprotein and a non-cleavable preprotein by Brix (1999)
  7. 10.1093/emboj/cdg532 / EMBO J. / Mitochondrial translocation contact sites: Separation of dynamic and stabilizing elements in formation of a TOM-TIM-preprotein supercomplex by Chacinska (2003)
  8. 10.1016/j.cell.2005.01.011 / Cell. / Mitochondrial presequence translocase: Switching between TOM tethering and motor recruitment involves Tim21 and Tim17 by Chacinska (2005)
  9. 10.1016/j.cell.2009.08.005 / Cell. / Importing mitochondrial proteins: Machineries and mechanisms by Chacinska (2009)
  10. 10.1128/MCB.00749-09 / Mol. Cell. Biol. / Distinct forms of mitochondrial TOM-TIM supercomplexes define signal-dependent states of preprotein sorting by Chacinska (2010)
  11. 10.1080/10715760903038432 / Free Radic. Res. / Mitochondrial reactive oxygen species originating from Romo1 exert an important role in normal cell cycle progression by regulating p27(Kip1) expression by Chung (2009)
  12. 10.1074/jbc.M805334200 / J. Biol. Chem. / Replicative senescence induced by Romo1-derived reactive oxygen species by Chung (2008)
  13. 10.1038/nbt.1511 / Nat. Biotechnol. / MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification by Cox (2008)
  14. 10.1016/0014-5793(93)80921-G / FEBS Lett. / Identification of MIM23, a putative component of the protein import machinery of the mitochondrial inner membrane by Dekker (1993)
  15. 10.1093/emboj/16.17.5408 / EMBO J. / The Tim core complex defines the number of mitochondrial translocation contact sites and can hold arrested preproteins in the absence of matrix Hsp70-Tim44 by Dekker (1997)
  16. 10.1016/j.cell.2011.06.004 / Cell. / Stepwise insertion and inversion of a type II signal anchor sequence in the ribosome-Sec61 translocon complex by Devaraneni (2011)
  17. 10.1091/mbc.E08-04-0402 / Mol. Biol. Cell. / The yeast Aac2 protein exists in physical association with the cytochrome bc1-COX supercomplex and the TIM23 machinery by Dienhart (2008)
  18. 10.1126/science.1127895 / Science. / Evolution of the molecular machines for protein import into mitochondria by Dolezal (2006)
  19. 10.1091/mbc.E05-06-0585 / Mol. Biol. Cell. / A genomewide screen for petite-negative yeast strains yields a new subunit of the i-AAA protease complex by Dunn (2006)
  20. 10.1083/jcb.122.5.1003 / J. Cell Biol. / MAS6 encodes an essential inner membrane component of the yeast mitochondrial protein import pathway by Emtage (1993)
  21. 10.1016/j.bbamem.2010.07.018 / Biochim. Biophys. Acta. / Structural insight into the mitochondrial protein import system by Endo (2011)
  22. 10.1016/0076-6879(91)94049-I / Methods Enzymol. / In vitro protein translocation across microsomal membranes of Saccharomyces cerevisiae by Garcia (1991)
  23. 10.1016/j.molcel.2011.09.025 / Mol. Cell. / Dual function of Sdh3 in the respiratory chain and TIM22 protein translocase of the mitochondrial inner membrane by Gebert (2011)
  24. 10.1091/mbc.11.11.3977 / Mol. Biol. Cell. / Membrane potential-driven protein import into mitochondria. The sorting sequence of cytochrome b(2) modulates the deltapsi-dependence of translocation of the matrix-targeting sequence by Geissler (2000)
  25. 10.1016/S0092-8674(02)01073-5 / Cell. / The mitochondrial presequence translocase: An essential role of Tim50 in directing preproteins to the import channel by Geissler (2002)
  26. 10.1074/jbc.M807041200 / J. Biol. Chem. / Interaction of Tim23 with Tim50 is essential for protein translocation by the mitochondrial TIM23 complex by Gevorkyan-Airapetov (2009)
  27. 10.1016/0092-8674(92)90292-K / Cell. / Cytochromes c1 and b2 are sorted to the intermembrane space of yeast mitochondria by a stop-transfer mechanism by Glick (1992)
  28. 10.1006/expr.2000.4564 / Exp. Parasitol. / Leishmania tarentolae: A parallel isolation of cytochrome bc(1) and cytochrome c oxidase by Horváth (2000)
  29. 10.1091/mbc.E07-12-1226 / Mol. Biol. Cell. / Mitochondrial protein import motor: Differential role of Tim44 in the recruitment of Pam17 and J-complex to the presequence translocase by Hutu (2008)
  30. 10.1074/mcp.M111.010462 / Mol. Cell. Proteomics. / Genome-wide characterization of miR-34a induced changes in protein and mRNA expression by a combined pulsed SILAC and microarray analysis by Kaller (2011)
  31. 10.1038/cdd.2010.19 / Cell Death Differ. / TNF-α-induced ROS production triggering apoptosis is directly linked to Romo1 and Bcl-X(L) by Kim (2010)
  32. 10.1146/annurev.cellbio.20.010403.105057 / Annu. Rev. Cell Dev. Biol. / New developments in mitochondrial assembly by Koehler (2004)
  33. 10.1007/s10495-009-0411-1 / Apoptosis. / Serum deprivation-induced reactive oxygen species production is mediated by Romo1 by Lee (2010)
  34. 10.1016/0014-5793(94)00669-5 / FEBS Lett. / Identification of the essential yeast protein MIM17, an integral mitochondrial inner membrane protein involved in protein import by Maarse (1994)
  35. 10.1074/jbc.M111.261040 / J. Biol. Chem. / Direct interaction of mitochondrial targeting presequences with purified components of the TIM23 protein complex by Marom (2011)
  36. 10.1083/jcb.200505126 / J. Cell Biol. / Proline residues of transmembrane domains determine the sorting of inner membrane proteins in mitochondria by Meier (2005)
  37. 10.1126/science.1127628 / Science. / Tim50 maintains the permeability barrier of the mitochondrial inner membrane by Meinecke (2006)
  38. {'key': '2023072302271641600_bib38', 'first-page': '33', 'article-title': 'Isolation of yeast mitochondria', 'volume': '313', 'author': 'Meisinger', 'year': '2006', 'journal-title': 'Methods Mol. Biol.'} / Methods Mol. Biol. / Isolation of yeast mitochondria by Meisinger (2006)
  39. 10.1074/jbc.C500135200 / J. Biol. Chem. / Role of Tim21 in mitochondrial translocation contact sites by Mokranjac (2005)
  40. 10.1091/mbc.E08-09-0934 / Mol. Biol. Cell. / Role of Tim50 in the transfer of precursor proteins from the outer to the inner membrane of mitochondria by Mokranjac (2009)
  41. 10.1146/annurev.biochem.76.052705.163409 / Annu. Rev. Biochem. / Translocation of proteins into mitochondria by Neupert (2007)
  42. 10.1074/mcp.M200025-MCP200 / Mol. Cell. Proteomics. / Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics by Ong (2002)
  43. {'key': '2023072302271641600_bib43', 'first-page': '191', 'article-title': 'Purification of the cytochrome bc1 complex from yeast', 'author': 'Palsdottir', 'year': '2003'} / Purification of the cytochrome bc1 complex from yeast by Palsdottir (2003)
  44. {'key': '2023072302271641600_bib44', 'first-page': '1469', 'article-title': 'Active remodelling of the TIM23 complex during translocation of preproteins into mitochondria', 'volume': '27', 'author': 'Popov-Celeketić', 'year': '2008', 'journal-title': 'EMBO J.'} / EMBO J. / Active remodelling of the TIM23 complex during translocation of preproteins into mitochondria by Popov-Celeketić (2008)
  45. 10.1038/embor.2011.72 / EMBO Rep. / Role of the import motor in insertion of transmembrane segments by the mitochondrial TIM23 complex by Popov-Čeleketić (2011)
  46. 10.1016/j.jmb.2011.06.020 / J. Mol. Biol. / Structural basis for the function of Tim50 in the mitochondrial presequence translocase by Qian (2011)
  47. 10.1016/0014-5793(90)81469-5 / FEBS Lett. / Polypeptides traverse the mitochondrial envelope in an extended state by Rassow (1990)
  48. 10.1126/science.1080945 / Science. / Protein insertion into the mitochondrial inner membrane by a twin-pore translocase by Rehling (2003)
  49. 10.1091/mbc.5.5.529 / Mol. Biol. Cell. / SMS1, a high-copy suppressor of the yeast mas6 mutant, encodes an essential inner membrane protein required for mitochondrial protein import by Ryan (1994)
  50. 10.1016/S0091-679X(01)65012-X / Methods Cell Biol. / Assaying protein import into mitochondria by Ryan (2001)
  51. 10.1074/jbc.M708440200 / J. Biol. Chem. / The F1F0-ATP synthase complex influences the assembly state of the cytochrome bc1-cytochrome oxidase supercomplex and its association with the TIM23 machinery by Saddar (2008)
  52. 10.1016/0003-2697(91)90094-A / Anal. Biochem. / Blue native electrophoresis for isolation of membrane protein complexes in enzymatically active form by Schägger (1991)
  53. 10.1074/jbc.272.47.29963 / J. Biol. Chem. / Functional cooperation and stoichiometry of protein translocases of the outer and inner membranes of mitochondria by Sirrenberg (1997)
  54. 10.1016/S0091-679X(06)80036-1 / Methods Cell Biol. / Import of proteins into mitochondria by Stojanovski (2007)
  55. 10.1083/jcb.200808068 / J. Cell Biol. / Tim23–Tim50 pair coordinates functions of translocators and motor proteins in mitochondrial protein import by Tamura (2009)
  56. 10.1074/jbc.273.16.9630 / J. Biol. Chem. / Expression of a plastidic ATP/ADP transporter gene in Escherichia coli leads to a functional adenine nucleotide transport system in the bacterial cytoplasmic membrane by Tjaden (1998)
  57. 10.1371/journal.pbio.0050231 / PLoS Biol. / Enlightening energy parasitism by analysis of an ATP/ADP transporter from chlamydiae by Trentmann (2007)
  58. 10.1038/nsb726 / Nat. Struct. Biol. / A presequence- and voltage-sensitive channel of the mitochondrial preprotein translocase formed by Tim23 by Truscott (2001)
  59. 10.1128/MCB.25.17.7449-7458.2005 / Mol. Cell. Biol. / Pam17 is required for architecture and translocation activity of the mitochondrial protein import motor by van der Laan (2005)
  60. 10.1016/j.cub.2006.10.025 / Curr. Biol. / A role for Tim21 in membrane-potential-dependent preprotein sorting in mitochondria by van der Laan (2006)
  61. 10.1038/ncb1635 / Nat. Cell Biol. / Motor-free mitochondrial presequence translocase drives membrane integration of preproteins by van der Laan (2007)
  62. 10.1016/j.cell.2009.07.045 / Cell. / Global analysis of the mitochondrial N-proteome identifies a processing peptidase critical for protein stability by Vögtle (2009)
  63. 10.1016/j.devcel.2011.08.026 / Dev. Cell. / Dual role of mitofilin in mitochondrial membrane organization and protein biogenesis by von der Malsburg (2011)
  64. 10.1002/j.1460-2075.1992.tb05584.x / EMBO J. / Role of ATP in the intramitochondrial sorting of cytochrome c1 and the adenine nucleotide translocator by Wachter (1992)
  65. 10.1083/jcb.200709087 / J. Cell Biol. / Sorting switch of mitochondrial presequence translocase involves coupling of motor module to respiratory chain by Wiedemann (2007)
  66. 10.1016/S0092-8674(02)01053-X / Cell. / Tim50 is a subunit of the TIM23 complex that links protein translocation across the outer and inner mitochondrial membranes by Yamamoto (2002)
  67. 10.1074/jbc.M708339200 / J. Biol. Chem. / Tom20 and Tom22 share the common signal recognition pathway in mitochondrial protein import by Yamano (2008)
  68. 10.1242/jcs.038513 / J. Cell Sci. / The novel conserved mitochondrial inner-membrane protein MTGM regulates mitochondrial morphology and cell proliferation by Zhao (2009)
Dates
Type When
Created 13 years, 3 months ago (May 21, 2012, 10:50 p.m.)
Deposited 2 years, 1 month ago (July 22, 2023, 10:27 p.m.)
Indexed 1 day, 13 hours ago (Aug. 29, 2025, 6:15 a.m.)
Issued 13 years, 3 months ago (May 21, 2012)
Published 13 years, 3 months ago (May 21, 2012)
Published Online 13 years, 3 months ago (May 21, 2012)
Published Print 13 years, 3 months ago (May 28, 2012)
Funders 0

None

@article{Gebert_2012, title={Mgr2 promotes coupling of the mitochondrial presequence translocase to partner complexes}, volume={197}, ISSN={0021-9525}, url={http://dx.doi.org/10.1083/jcb.201110047}, DOI={10.1083/jcb.201110047}, number={5}, journal={Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Gebert, Michael and Schrempp, Sandra G. and Mehnert, Carola S. and Heißwolf, Anna K. and Oeljeklaus, Silke and Ieva, Raffaele and Bohnert, Maria and von der Malsburg, Karina and Wiese, Sebastian and Kleinschroth, Thomas and Hunte, Carola and Meyer, Helmut E. and Haferkamp, Ilka and Guiard, Bernard and Warscheid, Bettina and Pfanner, Nikolaus and van der Laan, Martin}, year={2012}, month=may, pages={595–604} }