Home LiteratureArticle Details
PMID: 18039934 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Alternative function for the mitochondrial SAM complex in biogenesis of alpha-helical TOM proteins.

The Journal of cell biology ·Vol. 179 ·No. 5 ·2007-12-03 ·Pages 881-93

Stojanovski D, Guiard B, Kozjak-Pavlovic V, Pfanner N, Meisinger C

Abstract

The mitochondrial outer membrane contains two preprotein translocases: the general translocase of outer membrane (TOM) and the beta-barrel-specific sorting and assembly machinery (SAM). TOM functions as the central entry gate for nuclear-encoded proteins. The channel-forming Tom40 is a beta-barrel protein, whereas all Tom receptors and small Tom proteins are membrane anchored by a transmembrane alpha-helical segment in their N- or C-terminal portion. Synthesis of Tom precursors takes place in the cytosol, and their import occurs via preexisting TOM complexes. The precursor of Tom40 is then transferred to SAM for membrane insertion and assembly. Unexpectedly, we find that the biogenesis of alpha-helical Tom proteins with a membrane anchor in the C-terminal portion is SAM dependent. Each SAM protein is necessary for efficient membrane integration of the receptor Tom22, whereas assembly of the small Tom proteins depends on Sam37. Thus, the substrate specificity of SAM is not restricted to beta-barrel proteins but also includes the majority of alpha-helical Tom proteins.

MeSH Terms
Membrane Transport Proteins/metabolism Mitochondria/metabolism Mitochondrial Membrane Transport Proteins Mitochondrial Membranes/metabolism Mitochondrial Proteins/metabolism Mitochondrial Swelling Multiprotein Complexes/metabolism Mutation/genetics Protein Precursors/metabolism Protein Structure, Secondary Protein Subunits/metabolism Saccharomyces cerevisiae/cytology,metabolism Saccharomyces cerevisiae Proteins/chemistry,metabolism
Chemicals
Membrane Transport Proteins Mitochondrial Membrane Transport Proteins Mitochondrial Proteins Multiprotein Complexes Protein Precursors Protein Subunits Saccharomyces cerevisiae Proteins Sam35 protein, S cerevisiae TOM22 protein, S cerevisiae
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Stojanovski Diana
Institut für Biochemie und Molekularbiologie, Zentrum für Biochemie und Molekulare Zellforschung, Universität Freiburg, D-79104 Freiburg, Germany.
Guiard Bernard
Kozjak-Pavlovic Vera
Pfanner Nikolaus
Meisinger Chris
References (77)
77 references, click to expand
  1. Mdv1p is a WD repeat protein that interacts with the dynamin-related GTPase, Dnm1p, to trigger mitochondrial division.
    J Cell Biol. 2000 Oct 16;151(2):353-66 PMID: 11038182
  2. Signal-anchor domains of proteins of the outer membrane of mitochondria: structural and functional characteristics.
    J Biol Chem. 2003 Oct 24;278(43):42064-71 PMID: 12917440
  3. Dissection of the mitochondrial import and assembly pathway for human Tom40.
    J Biol Chem. 2005 Mar 25;280(12):11535-43 PMID: 15644312
  4. Proteomic analysis of the yeast mitochondrial outer membrane reveals accumulation of a subclass of preproteins.
    Mol Biol Cell. 2006 Mar;17(3):1436-50 PMID: 16407407
  5. Folding of a bacterial outer membrane protein during passage through the periplasm.
    EMBO J. 1997 Jul 16;16(14):4295-301 PMID: 9250673
  6. Targeting and assembly of mitochondrial tail-anchored protein Tom5 to the TOM complex depend on a signal distinct from that of tail-anchored proteins dispersed in the membrane.
    J Biol Chem. 2003 Oct 17;278(42):41462-71 PMID: 12896971
  7. Machinery for protein sorting and assembly in the mitochondrial outer membrane.
    Nature. 2003 Jul 31;424(6948):565-71 PMID: 12891361
  8. Tob38, a novel essential component in the biogenesis of beta-barrel proteins of mitochondria.
    EMBO Rep. 2004 Jul;5(7):704-9 PMID: 15205677
  9. Biogenesis of the protein import channel Tom40 of the mitochondrial outer membrane: intermembrane space components are involved in an early stage of the assembly pathway.
    J Biol Chem. 2004 Apr 30;279(18):18188-94 PMID: 14978039
  10. Dnm1p GTPase-mediated mitochondrial fission is a multi-step process requiring the novel integral membrane component Fis1p.
    J Cell Biol. 2000 Oct 16;151(2):367-80 PMID: 11038183
  11. Integral membrane proteins in the mitochondrial outer membrane of Saccharomyces cerevisiae.
    FEBS J. 2006 Apr;273(7):1507-15 PMID: 16689936
  12. Chaperones: inserting beta barrels into membranes.
    Curr Biol. 2004 Mar 9;14(5):R207-9 PMID: 15028240
  13. Biogenesis of beta-barrel membrane proteins of mitochondria.
    Trends Biochem Sci. 2005 Oct;30(10):575-82 PMID: 16126389
  14. Protein translocase of the outer mitochondrial membrane: role of import receptors in the structural organization of the TOM complex.
    J Mol Biol. 2002 Feb 22;316(3):657-66 PMID: 11866524
  15. Biogenesis of Tom40, core component of the TOM complex of mitochondria.
    J Cell Biol. 1999 Jul 26;146(2):321-31 PMID: 10427088
  16. Assembly of the TOB complex of mitochondria.
    J Biol Chem. 2005 Feb 25;280(8):6434-40 PMID: 15590639
  17. Tom5 functionally links mitochondrial preprotein receptors to the general import pore.
    Nature. 1997 Jul 10;388(6638):195-200 PMID: 9217162
  18. Molecular architecture and function of the Omp85 family of proteins.
    Mol Microbiol. 2005 Dec;58(5):1216-25 PMID: 16313611
  19. Integrative analysis of the mitochondrial proteome in yeast.
    PLoS Biol. 2004 Jun;2(6):e160 PMID: 15208715
  20. Opening the door to mitochondrial protein import.
    Nat Struct Biol. 2001 Dec;8(12):1008-10 PMID: 11723465
  21. An import signal in the cytosolic domain of the Neurospora mitochondrial outer membrane protein TOM22.
    J Biol Chem. 1998 May 8;273(19):11527-32 PMID: 9565567
  22. Targeting and assembly of rat mitochondrial translocase of outer membrane 22 (TOM22) into the TOM complex.
    J Biol Chem. 2004 May 14;279(20):21223-32 PMID: 14985332
  23. Signal-anchored proteins follow a unique insertion pathway into the outer membrane of mitochondria.
    J Biol Chem. 2005 Jan 7;280(1):48-53 PMID: 15501820
  24. The structure of bacterial outer membrane proteins.
    Biochim Biophys Acta. 2002 Oct 11;1565(2):308-17 PMID: 12409203
  25. Multiple functions of tail-anchor domains of mitochondrial outer membrane proteins.
    FEBS Lett. 2003 Dec 18;555(3):511-5 PMID: 14675765
  26. Evolution of the molecular machines for protein import into mitochondria.
    Science. 2006 Jul 21;313(5785):314-8 PMID: 16857931
  27. Isolation of intracellular membranes by means of sodium carbonate treatment: application to endoplasmic reticulum.
    J Cell Biol. 1982 Apr;93(1):97-102 PMID: 7068762
  28. Import of proteins into mitochondria.
    Methods Cell Biol. 2007;80:783-806 PMID: 17445722
  29. Targeting of the master receptor MOM19 to mitochondria.
    Science. 1991 Dec 13;254(5038):1659-62 PMID: 1661031
  30. Characterization of the signal that directs Tom20 to the mitochondrial outer membrane.
    J Cell Biol. 2000 Oct 16;151(2):277-88 PMID: 11038175
  31. The major 45-kDa protein of the yeast mitochondrial outer membrane is not essential for cell growth or mitochondrial function.
    J Biol Chem. 1989 Dec 15;264(35):21091-6 PMID: 2687271
  32. Biogenesis of ISP6, a small carboxyl-terminal anchored protein of the receptor complex of the mitochondrial outer membrane.
    J Biol Chem. 1995 Mar 10;270(10):5674-9 PMID: 7890690
  33. Mitochondrial protein sorting: differentiation of beta-barrel assembly by Tom7-mediated segregation of Mdm10.
    J Biol Chem. 2006 Aug 11;281(32):22819-26 PMID: 16760475
  34. Insertion of MOM22 into the mitochondrial outer membrane strictly depends on surface receptors.
    FEBS Lett. 1993 Apr 26;321(2-3):197-200 PMID: 8477850
  35. Evolutionary conservation of biogenesis of beta-barrel membrane proteins.
    Nature. 2003 Dec 18;426(6968):862-6 PMID: 14685243
  36. Mitochondrial import and the twin-pore translocase.
    Nat Rev Mol Cell Biol. 2004 Jul;5(7):519-30 PMID: 15232570
  37. Structural requirements of Tom40 for assembly into preexisting TOM complexes of mitochondria.
    Mol Biol Cell. 2001 May;12(5):1189-98 PMID: 11359915
  38. An essential role of Sam50 in the protein sorting and assembly machinery of the mitochondrial outer membrane.
    J Biol Chem. 2003 Dec 5;278(49):48520-3 PMID: 14570913
  39. Protein import channel of the outer mitochondrial membrane: a highly stable Tom40-Tom22 core structure differentially interacts with preproteins, small tom proteins, and import receptors.
    Mol Cell Biol. 2001 Apr;21(7):2337-48 PMID: 11259583
  40. Mas37p, a novel receptor subunit for protein import into mitochondria.
    J Cell Biol. 1995 Apr;129(1):25-34 PMID: 7698990
  41. The proteome of Saccharomyces cerevisiae mitochondria.
    Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13207-12 PMID: 14576278
  42. Role of a highly conserved bacterial protein in outer membrane protein assembly.
    Science. 2003 Jan 10;299(5604):262-5 PMID: 12522254
  43. Proteome analysis of mitochondrial outer membrane from Neurospora crassa.
    Proteomics. 2006 Jan;6(1):72-80 PMID: 16294304
  44. Fzo1p is a mitochondrial outer membrane protein essential for the biogenesis of functional mitochondria in Saccharomyces cerevisiae.
    J Biol Chem. 1998 Aug 7;273(32):20150-5 PMID: 9685359
  45. Assembly of Tom6 and Tom7 into the TOM core complex of Neurospora crassa.
    J Biol Chem. 2001 May 25;276(21):17679-85 PMID: 11278536
  46. The Tim8-Tim13 complex of Neurospora crassa functions in the assembly of proteins into both mitochondrial membranes.
    J Biol Chem. 2004 Mar 26;279(13):12396-405 PMID: 14722057
  47. UGO1 encodes an outer membrane protein required for mitochondrial fusion.
    J Cell Biol. 2001 Mar 19;152(6):1123-34 PMID: 11257114
  48. Targeting of tail-anchored proteins to yeast mitochondria in vivo.
    FEBS Lett. 1999 May 28;451(3):243-8 PMID: 10371198
  49. Advances in understanding bacterial outer-membrane biogenesis.
    Nat Rev Microbiol. 2006 Jan;4(1):57-66 PMID: 16357861
  50. The morphology proteins Mdm12/Mmm1 function in the major beta-barrel assembly pathway of mitochondria.
    EMBO J. 2007 May 2;26(9):2229-39 PMID: 17410204
  51. The three modules of ADP/ATP carrier cooperate in receptor recruitment and translocation into mitochondria.
    EMBO J. 2001 Mar 1;20(5):951-60 PMID: 11230119
  52. Conserved roles of Sam50 and metaxins in VDAC biogenesis.
    EMBO Rep. 2007 Jun;8(6):576-82 PMID: 17510655
  53. Multistep assembly of the protein import channel of the mitochondrial outer membrane.
    Nat Struct Biol. 2001 Apr;8(4):361-70 PMID: 11276259
  54. Finding the right organelle. Targeting signals in mitochondrial outer-membrane proteins.
    EMBO Rep. 2003 Oct;4(10):948-52 PMID: 14528265
  55. Functional cooperation and separation of translocators in protein import into mitochondria, the double-membrane bounded organelles.
    J Cell Sci. 2003 Aug 15;116(Pt 16):3259-67 PMID: 12857785
  56. The Omp85 family of proteins is essential for outer membrane biogenesis in mitochondria and bacteria.
    J Cell Biol. 2004 Jan 5;164(1):19-24 PMID: 14699090
  57. Import and assembly of proteins into mitochondria of mammalian cells.
    Biochim Biophys Acta. 2002 Sep 2;1592(1):97-105 PMID: 12191772
  58. Membrane protein insertion: mixing eukaryotic and prokaryotic concepts.
    EMBO Rep. 2005 Nov;6(11):1023-7 PMID: 16264426
  59. Biogenesis of the Gram-negative bacterial outer membrane.
    Curr Opin Microbiol. 2004 Dec;7(6):610-6 PMID: 15556033
  60. Sam35 of the mitochondrial protein sorting and assembly machinery is a peripheral outer membrane protein essential for cell viability.
    J Biol Chem. 2004 May 21;279(21):22781-5 PMID: 15067005
  61. Two novel proteins in the mitochondrial outer membrane mediate beta-barrel protein assembly.
    J Cell Biol. 2004 Aug 30;166(5):621-7 PMID: 15326197
  62. Yeast Miro GTPase, Gem1p, regulates mitochondrial morphology via a novel pathway.
    J Cell Biol. 2004 Oct 11;167(1):87-98 PMID: 15479738
  63. Tom40 forms the hydrophilic channel of the mitochondrial import pore for preproteins [see comment].
    Nature. 1998 Oct 1;395(6701):516-21 PMID: 9774109
  64. Mitochondrial fusion in yeast requires the transmembrane GTPase Fzo1p.
    J Cell Biol. 1998 Oct 19;143(2):359-73 PMID: 9786948
  65. A railroad switch in mitochondrial protein import.
    Mol Cell. 2005 Apr 15;18(2):145-6 PMID: 15837417
  66. A conserved proline residue is present in the transmembrane-spanning domain of Tom7 and other tail-anchored protein subunits of the TOM translocase.
    FEBS Lett. 2002 Mar 13;514(2-3):347-50 PMID: 11943179
  67. Folding intermediates of a beta-barrel membrane protein. Kinetic evidence for a multi-step membrane insertion mechanism.
    Biochemistry. 1996 Oct 8;35(40):12993-3000 PMID: 8855933
  68. Toward the complete yeast mitochondrial proteome: multidimensional separation techniques for mitochondrial proteomics.
    J Proteome Res. 2006 Jul;5(7):1543-54 PMID: 16823961
  69. New developments in mitochondrial assembly.
    Annu Rev Cell Dev Biol. 2004;20:309-35 PMID: 15473843
  70. Assembling the mitochondrial outer membrane.
    Nat Struct Mol Biol. 2004 Nov;11(11):1044-8 PMID: 15523480
  71. Molecular chaperones Hsp90 and Hsp70 deliver preproteins to the mitochondrial import receptor Tom70.
    Cell. 2003 Jan 10;112(1):41-50 PMID: 12526792
  72. Ugo1p is a multipass transmembrane protein with a single carrier domain required for mitochondrial fusion.
    Traffic. 2007 May;8(5):500-11 PMID: 17451553
  73. Translocation of proteins into mitochondria.
    Annu Rev Biochem. 2007;76:723-49 PMID: 17263664
  74. Tom40, the import channel of the mitochondrial outer membrane, plays an active role in sorting imported proteins.
    EMBO J. 2003 May 15;22(10):2380-6 PMID: 12743032
  75. How does the TOM complex mediate insertion of precursor proteins into the mitochondrial outer membrane?
    J Cell Biol. 2005 Nov 7;171(3):419-23 PMID: 16260501
  76. The mitochondrial morphology protein Mdm10 functions in assembly of the preprotein translocase of the outer membrane.
    Dev Cell. 2004 Jul;7(1):61-71 PMID: 15239954
  77. Alternative splicing gives rise to different isoforms of the Neurospora crassa Tob55 protein that vary in their ability to insert beta-barrel proteins into the outer mitochondrial membrane.
    Genetics. 2007 Sep;177(1):137-49 PMID: 17660559
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
Published
2007-12-03
Epub
2007-00-26
Pages
881-93
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2099199
Subset
IM
Corrections
ErratumIn
-
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]