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PMID: 19752025 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Coassembly of Mgm1 isoforms requires cardiolipin and mediates mitochondrial inner membrane fusion.

The Journal of cell biology ·Vol. 186 ·No. 6 ·2009-09-21 ·Pages 793-803

DeVay RM, Dominguez-Ramirez L, Lackner LL, Hoppins S, Stahlberg H, Nunnari J

Abstract

Two dynamin-related protein (DRP) families are essential for fusion of the outer and inner mitochondrial membranes, Fzo1 (yeast)/Mfn1/Mfn2 (mammals) and Mgm1 (yeast)/Opa1 (mammals), respectively. Fzo1/Mfns possess two medial transmembrane domains, which place their critical GTPase and coiled-coil domains in the cytosol. In contrast, Mgm1/Opa1 are present in cells as long (l) isoforms that are anchored via the N terminus to the inner membrane, and short (s) isoforms were predicted to be soluble in the intermembrane space. We addressed the roles of Mgm1 isoforms and how DRPs function in membrane fusion. Our analysis indicates that in the absence of a membrane, l- and s-Mgm1 both exist as inactive GTPase monomers, but that together in trans they form a functional dimer in a cardiolipin-dependent manner that is the building block for higher-order assemblies.

MeSH Terms
Cardiolipins/metabolism GTP-Binding Proteins/chemistry,genetics,metabolism Gene Expression Regulation, Fungal Guanosine Triphosphate/metabolism Hydrolysis Kinetics Liposomes Membrane Fusion Mitochondria/metabolism Mitochondrial Membranes/metabolism Mitochondrial Proteins/chemistry,genetics,metabolism Models, Molecular Mutation Protein Conformation Protein Isoforms Protein Multimerization Recombinant Fusion Proteins/metabolism Saccharomyces cerevisiae/genetics,growth & development,metabolism Saccharomyces cerevisiae Proteins/chemistry,genetics,metabolism Structure-Activity Relationship
Chemicals
Cardiolipins Liposomes MGM1 protein, S cerevisiae Mitochondrial Proteins Protein Isoforms Recombinant Fusion Proteins Saccharomyces cerevisiae Proteins Guanosine Triphosphate GTP-Binding Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
DeVay Rachel M
Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616, USA.
Dominguez-Ramirez Lenin
Lackner Laura L
Hoppins Suzanne
Stahlberg Henning
Nunnari Jodi
References (45)
45 references, click to expand
  1. Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae.
    Yeast. 1998 Jul;14(10):953-61 PMID: 9717241
  2. MRC image processing programs.
    J Struct Biol. 1996 Jan-Feb;116(1):9-16 PMID: 8742717
  3. Mitochondrial inner-membrane fusion and crista maintenance requires the dynamin-related GTPase Mgm1.
    Cell. 2006 Oct 20;127(2):383-95 PMID: 17055438
  4. 2dx--user-friendly image processing for 2D crystals.
    J Struct Biol. 2007 Jan;157(1):64-72 PMID: 17055742
  5. Mitochondrial outer and inner membrane fusion requires a modified carrier protein.
    J Cell Biol. 2009 Feb 23;184(4):569-81 PMID: 19237599
  6. 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
  7. Mitochondrial rhomboid PARL regulates cytochrome c release during apoptosis via OPA1-dependent cristae remodeling.
    Cell. 2006 Jul 14;126(1):163-75 PMID: 16839884
  8. Development and testing of an automated approach to protein docking.
    Proteins. 2005 Aug 1;60(2):296-301 PMID: 15981259
  9. Dynamin family of mechanoenzymes.
    Curr Opin Cell Biol. 2001 Aug;13(4):454-60 PMID: 11454452
  10. Quality assessment of multiple alignment programs.
    FEBS Lett. 2002 Oct 2;529(1):126-30 PMID: 12354624
  11. Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity.
    J Cell Sci. 2004 Dec 15;117(Pt 26):6535-46 PMID: 15572413
  12. Cells lacking Pcp1p/Ugo2p, a rhomboid-like protease required for Mgm1p processing, lose mtDNA and mitochondrial structure in a Dnm1p-dependent manner, but remain competent for mitochondrial fusion.
    Biochem Biophys Res Commun. 2003 Aug 22;308(2):276-83 PMID: 12901865
  13. Protein-protein docking with simultaneous optimization of rigid-body displacement and side-chain conformations.
    J Mol Biol. 2003 Aug 1;331(1):281-99 PMID: 12875852
  14. Isolation and biochemical characterization of organelles from the yeast, Saccharomyces cerevisiae.
    Yeast. 1995 May;11(6):493-536 PMID: 7645343
  15. Determination of molecular weights and frictional ratios of proteins in impure systems by use of gel filtration and density gradient centrifugation. Application to crude preparations of sulfite and hydroxylamine reductases.
    Biochim Biophys Acta. 1966 Feb 7;112(2):346-62 PMID: 5329026
  16. OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion.
    Cell. 2006 Jul 14;126(1):177-89 PMID: 16839885
  17. 2dx_merge: data management and merging for 2D crystal images.
    J Struct Biol. 2007 Dec;160(3):375-84 PMID: 17967545
  18. OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L.
    J Cell Biol. 2007 Aug 27;178(5):749-55 PMID: 17709429
  19. Regulation of the mitochondrial dynamin-like protein Opa1 by proteolytic cleavage.
    J Cell Biol. 2007 Aug 27;178(5):757-64 PMID: 17709430
  20. Improvement of the GenTHREADER method for genomic fold recognition.
    Bioinformatics. 2003 May 1;19(7):874-81 PMID: 12724298
  21. Mdv1 interacts with assembled dnm1 to promote mitochondrial division.
    J Biol Chem. 2006 Jan 27;281(4):2177-83 PMID: 16272155
  22. Comparative protein structure modeling of genes and genomes.
    Annu Rev Biophys Biomol Struct. 2000;29:291-325 PMID: 10940251
  23. Two-dimensional crystallization on lipid layer: A successful approach for membrane proteins.
    J Struct Biol. 1999 Aug;127(1):44-52 PMID: 10479616
  24. UCSF Chimera--a visualization system for exploratory research and analysis.
    J Comput Chem. 2004 Oct;25(13):1605-12 PMID: 15264254
  25. Dnm1 forms spirals that are structurally tailored to fit mitochondria.
    J Cell Biol. 2005 Sep 26;170(7):1021-7 PMID: 16186251
  26. Lipid topology and physical properties of the outer mitochondrial membrane of the yeast, Saccharomyces cerevisiae.
    Biochim Biophys Acta. 1988 Dec 22;946(2):227-34 PMID: 3061466
  27. Processing of Mgm1 by the rhomboid-type protease Pcp1 is required for maintenance of mitochondrial morphology and of mitochondrial DNA.
    J Biol Chem. 2003 Jul 25;278(30):27781-8 PMID: 12707284
  28. Mitochondrial fusion intermediates revealed in vitro.
    Science. 2004 Sep 17;305(5691):1747-52 PMID: 15297626
  29. Rapid purification of native dynamin I and colorimetric GTPase assay.
    Methods Enzymol. 2005;404:556-69 PMID: 16413300
  30. Structural basis of mitochondrial tethering by mitofusin complexes.
    Science. 2004 Aug 6;305(5685):858-62 PMID: 15297672
  31. The dynamin-related protein Mgm1p assembles into oligomers and hydrolyzes GTP to function in mitochondrial membrane fusion.
    Biochemistry. 2009 Mar 3;48(8):1774-84 PMID: 19236101
  32. Mitochondrial fusion in yeast requires the transmembrane GTPase Fzo1p.
    J Cell Biol. 1998 Oct 19;143(2):359-73 PMID: 9786948
  33. Domain interactions within Fzo1 oligomers are essential for mitochondrial fusion.
    J Biol Chem. 2006 Jun 16;281(24):16599-606 PMID: 16624808
  34. A bacterial dynamin-like protein.
    Nature. 2006 Dec 7;444(7120):766-9 PMID: 17122778
  35. Import of lipids into mitochondria.
    Prog Lipid Res. 1997 Sep;36(2-3):103-30 PMID: 9624424
  36. The intramitochondrial dynamin-related GTPase, Mgm1p, is a component of a protein complex that mediates mitochondrial fusion.
    J Cell Biol. 2003 Feb 3;160(3):303-11 PMID: 12566426
  37. The machines that divide and fuse mitochondria.
    Annu Rev Biochem. 2007;76:751-80 PMID: 17362197
  38. A novel two-step mechanism for removal of a mitochondrial signal sequence involves the mAAA complex and the putative rhomboid protease Pcp1.
    J Mol Biol. 2002 Nov 8;323(5):835-43 PMID: 12417197
  39. Regulation of mitochondrial morphology through proteolytic cleavage of OPA1.
    EMBO J. 2006 Jul 12;25(13):2966-77 PMID: 16778770
  40. Alternative topogenesis of Mgm1 and mitochondrial morphology depend on ATP and a functional import motor.
    J Cell Biol. 2004 Apr 26;165(2):167-73 PMID: 15096522
  41. Proteolytic processing of OPA1 links mitochondrial dysfunction to alterations in mitochondrial morphology.
    J Biol Chem. 2006 Dec 8;281(49):37972-9 PMID: 17003040
  42. It takes two to tango: regulation of G proteins by dimerization.
    Nat Rev Mol Cell Biol. 2009 Jun;10(6):423-9 PMID: 19424291
  43. Distinct roles of the two isoforms of the dynamin-like GTPase Mgm1 in mitochondrial fusion.
    FEBS Lett. 2009 Jul 7;583(13):2237-43 PMID: 19505460
  44. Mitochondrial membrane remodelling regulated by a conserved rhomboid protease.
    Nature. 2003 May 29;423(6939):537-41 PMID: 12774122
  45. The dynamin middle domain is critical for tetramerization and higher-order self-assembly.
    EMBO J. 2007 Jan 24;26(2):559-66 PMID: 17170701
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.200906098
Published
2009-09-21
Epub
2009-00-14
Pages
793-803
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2753158
Subset
IM
Grants
NCRR NIH HHS · P41 RR-01081 · United States
NIGMS NIH HHS · R01 GM062942 · United States
NIGMS NIH HHS · U54GM074929 · United States
NIGMS NIH HHS · 1F32GM078749 · United States
Howard Hughes Medical Institute · S-HHMI01-GSRRD · United States
NIGMS NIH HHS · U54 GM074929 · United States
NIGMS NIH HHS · F32 GM078749 · United States
NCRR NIH HHS · P41 RR001081 · United States
NIGMS NIH HHS · R01GM062942 · United States
External Links
PubMed source DOI: 10.1083/jcb.200906098 PMC Full Text View journal details
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