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PMID: 15479738 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Yeast Miro GTPase, Gem1p, regulates mitochondrial morphology via a novel pathway.

The Journal of cell biology ·Vol. 167 ·No. 1 ·2004-10-11 ·Pages 87-98

Frederick RL, McCaffery JM, Cunningham KW, Okamoto K, Shaw JM

Abstract

Cell signaling events elicit changes in mitochondrial shape and activity. However, few mitochondrial proteins that interact with signaling pathways have been identified. Candidates include the conserved mitochondrial Rho (Miro) family of proteins, which contain two GTPase domains flanking a pair of calcium-binding EF-hand motifs. We show that Gem1p (yeast Miro; encoded by YAL048C) is a tail-anchored outer mitochondrial membrane protein. Cells lacking Gem1p contain collapsed, globular, or grape-like mitochondria. We demonstrate that Gem1p is not an essential component of characterized pathways that regulate mitochondrial dynamics. Genetic studies indicate both GTPase domains and EF-hand motifs, which are exposed to the cytoplasm, are required for Gem1p function. Although overexpression of a mutant human Miro protein caused increased apoptotic activity in cultured cells (Fransson et al., 2003. J. Biol. Chem. 278:6495-6502), Gem1p is not required for pheromone-induced yeast cell death. Thus, Gem1p defines a novel mitochondrial morphology pathway which may integrate cell signaling events with mitochondrial dynamics.

MeSH Terms
Actins/metabolism Amino Acid Motifs Amino Acid Sequence Apoptosis Cytoplasm/metabolism Cytoskeleton/metabolism DNA, Mitochondrial/metabolism GTP Phosphohydrolases/metabolism Glucose/metabolism Glycerol/metabolism Image Processing, Computer-Assisted Intracellular Membranes/metabolism Microscopy, Electron, Transmission Mitochondria/metabolism Molecular Sequence Data Multigene Family Mutation Pheromones/metabolism Plasmids/metabolism Protein Structure, Tertiary Saccharomyces cerevisiae/metabolism Saccharomyces cerevisiae Proteins/genetics,physiology Sequence Homology, Amino Acid Signal Transduction Temperature
Chemicals
Actins DNA, Mitochondrial GEM1 protein, S cerevisiae Pheromones Saccharomyces cerevisiae Proteins GTP Phosphohydrolases Glucose Glycerol
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Frederick Rebecca L
Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
McCaffery J Michael
Cunningham Kyle W
Okamoto Koji
Shaw Janet M
References (76)
76 references, click to expand
  1. Mitochondrial dynamics in mammals.
    Curr Top Dev Biol. 2004;59:119-44 PMID: 14975249
  2. Interplay between mitochondria and cellular calcium signalling.
    Mol Cell Biochem. 2004 Jan-Feb;256-257(1-2):209-18 PMID: 14977182
  3. Mmm2p, a mitochondrial outer membrane protein required for yeast mitochondrial shape and maintenance of mtDNA nucleoids.
    J Cell Biol. 2004 Mar 1;164(5):677-88 PMID: 14981098
  4. Rho-family GTPases: it's not only Rac and Rho (and I like it).
    J Cell Sci. 2004 Mar 15;117(Pt 8):1301-12 PMID: 15020670
  5. Yeast cell death during DNA damage arrest is independent of caspase or reactive oxygen species.
    J Cell Biol. 2004 Aug 2;166(3):311-6 PMID: 15289493
  6. Visualization of yeast mitochondrial DNA with the fluorescent stain "DAPI".
    Methods Enzymol. 1979;56:728-33 PMID: 459889
  7. Mutant ras-encoded proteins with altered nucleotide binding exert dominant biological effects.
    Proc Natl Acad Sci U S A. 1986 Feb;83(4):952-6 PMID: 3513168
  8. The cytoplasmic protein GAP is implicated as the target for regulation by the ras gene product.
    Nature. 1988 Apr 7;332(6164):548-51 PMID: 2833702
  9. Inhibition of NIH 3T3 cell proliferation by a mutant ras protein with preferential affinity for GDP.
    Mol Cell Biol. 1988 Aug;8(8):3235-43 PMID: 3145408
  10. Essential role for induced Ca2+ influx followed by [Ca2+]i rise in maintaining viability of yeast cells late in the mating pheromone response pathway. A study of [Ca2+]i in single Saccharomyces cerevisiae cells with imaging of fura-2.
    J Biol Chem. 1990 Aug 5;265(22):13391-9 PMID: 2198292
  11. The GTPase superfamily: conserved structure and molecular mechanism.
    Nature. 1991 Jan 10;349(6305):117-27 PMID: 1898771
  12. Targeting, disruption, replacement, and allele rescue: integrative DNA transformation in yeast.
    Methods Enzymol. 1991;194:281-301 PMID: 2005793
  13. Actin and myosin function in directed vacuole movement during cell division in Saccharomyces cerevisiae.
    J Cell Biol. 1996 Dec;135(6 Pt 1):1535-49 PMID: 8978821
  14. Mdm12p, a component required for mitochondrial inheritance that is conserved between budding and fission yeast.
    J Cell Biol. 1997 Feb 10;136(3):545-53 PMID: 9024686
  15. An essential role of the yeast pheromone-induced Ca2+ signal is to activate calcineurin.
    Mol Biol Cell. 1997 Feb;8(2):263-77 PMID: 9190206
  16. The yeast gene, MDM20, is necessary for mitochondrial inheritance and organization of the actin cytoskeleton.
    J Cell Biol. 1997 Apr 7;137(1):141-53 PMID: 9105043
  17. Mitochondrial transmission during mating in Saccharomyces cerevisiae is determined by mitochondrial fusion and fission and the intramitochondrial segregation of mitochondrial DNA.
    Mol Biol Cell. 1997 Jul;8(7):1233-42 PMID: 9243504
  18. Interaction between mitochondria and the actin cytoskeleton in budding yeast requires two integral mitochondrial outer membrane proteins, Mmm1p and Mdm10p.
    J Cell Biol. 1998 Jun 15;141(6):1371-81 PMID: 9628893
  19. The dynamin-related GTPase, Dnm1p, controls mitochondrial morphology in yeast.
    J Cell Biol. 1998 Oct 19;143(2):333-49 PMID: 9786946
  20. Mitochondrial fusion in yeast requires the transmembrane GTPase Fzo1p.
    J Cell Biol. 1998 Oct 19;143(2):359-73 PMID: 9786948
  21. Mitochondrial dynamics in yeast.
    Annu Rev Cell Dev Biol. 1998;14:265-303 PMID: 9891785
  22. The machinery of mitochondrial inheritance and behavior.
    Science. 1999 Mar 5;283(5407):1493-7 PMID: 10066164
  23. The open reading frame YAL048c affects the secretion of proteinase A in S. cerevisiae.
    Yeast. 1999 Mar 30;15(5):427-34 PMID: 10220001
  24. Division versus fusion: Dnm1p and Fzo1p antagonistically regulate mitochondrial shape.
    J Cell Biol. 1999 Nov 15;147(4):699-706 PMID: 10562274
  25. Yeast has homologs (CNA1 and CNA2 gene products) of mammalian calcineurin, a calmodulin-regulated phosphoprotein phosphatase.
    Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7376-80 PMID: 1651503
  26. Regulatory subunit (CNB1 gene product) of yeast Ca2+/calmodulin-dependent phosphoprotein phosphatases is required for adaptation to pheromone.
    Mol Cell Biol. 1992 Aug;12(8):3460-9 PMID: 1321337
  27. Calcineurin mediates inhibition by FK506 and cyclosporin of recovery from alpha-factor arrest in yeast.
    Nature. 1992 Dec 17;360(6405):682-4 PMID: 1281518
  28. DiOC6 staining reveals organelle structure and dynamics in living yeast cells.
    Cell Motil Cytoskeleton. 1993;25(2):111-28 PMID: 7686821
  29. Actin structure and function: roles in mitochondrial organization and morphogenesis in budding yeast and identification of the phalloidin-binding site.
    Mol Biol Cell. 1993 Dec;4(12):1277-94 PMID: 8167410
  30. Regulation of mitochondrial morphology and inheritance by Mdm10p, a protein of the mitochondrial outer membrane.
    J Cell Biol. 1994 Sep;126(6):1361-73 PMID: 8089171
  31. MMM1 encodes a mitochondrial outer membrane protein essential for establishing and maintaining the structure of yeast mitochondria.
    J Cell Biol. 1994 Sep;126(6):1375-91 PMID: 8089172
  32. Evolution of the EF-hand family of proteins.
    Annu Rev Biophys Biomol Struct. 1994;23:473-507 PMID: 7919790
  33. Yeast mitochondria contain ATP-sensitive, reversible actin-binding activity.
    Mol Biol Cell. 1994 Jul;5(7):807-18 PMID: 7812049
  34. Ca2+-calmodulin promotes survival of pheromone-induced growth arrest by activation of calcineurin and Ca2+-calmodulin-dependent protein kinase.
    Mol Cell Biol. 1996 Sep;16(9):4824-31 PMID: 8756641
  35. Calcium binding and conformational response in EF-hand proteins.
    Trends Biochem Sci. 1996 Jan;21(1):14-7 PMID: 8848832
  36. Multilamellar endosome-like compartment accumulates in the yeast vps28 vacuolar protein sorting mutant.
    Mol Biol Cell. 1996 Jun;7(6):985-99 PMID: 8817003
  37. The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast.
    Nat Cell Biol. 1999 Sep;1(5):298-304 PMID: 10559943
  38. Diversity of conformational states and changes within the EF-hand protein superfamily.
    Proteins. 1999 Nov 15;37(3):499-507 PMID: 10591109
  39. Calcium signalling: a historical account, recent developments and future perspectives.
    Cell Mol Life Sci. 2000 Mar;57(3):354-70 PMID: 10823237
  40. Mutants affecting the structure of the cortical endoplasmic reticulum in Saccharomyces cerevisiae.
    J Cell Biol. 2000 Aug 7;150(3):461-74 PMID: 10931860
  41. Suppressors of mdm20 in yeast identify new alleles of ACT1 and TPM1 predicted to enhance actin-tropomyosin interactions.
    Genetics. 2000 Oct;156(2):523-34 PMID: 11014803
  42. Gag3p, an outer membrane protein required for fission of mitochondrial tubules.
    J Cell Biol. 2000 Oct 16;151(2):333-40 PMID: 11038180
  43. 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
  44. 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
  45. EF-hand calcium-binding proteins.
    Curr Opin Struct Biol. 2000 Dec;10(6):637-43 PMID: 11114499
  46. Yeast mitochondrial dynamics: fusion, division, segregation, and shape.
    Microsc Res Tech. 2000 Dec 15;51(6):573-83 PMID: 11169859
  47. Division of mitochondria requires a novel DNM1-interacting protein, Net2p.
    Mol Biol Cell. 2001 Feb;12(2):309-21 PMID: 11179417
  48. Targeting of C-terminal (tail)-anchored proteins: understanding how cytoplasmic activities are anchored to intracellular membranes.
    Traffic. 2001 Jan;2(1):66-71 PMID: 11208169
  49. Mitochondrial division: New partners in membrane pinching.
    Curr Biol. 2001 Jan 23;11(2):R67-70 PMID: 11231145
  50. UGO1 encodes an outer membrane protein required for mitochondrial fusion.
    J Cell Biol. 2001 Mar 19;152(6):1123-34 PMID: 11257114
  51. Mmm1p, a mitochondrial outer membrane protein, is connected to mitochondrial DNA (mtDNA) nucleoids and required for mtDNA stability.
    J Cell Biol. 2001 Jan 22;152(2):401-10 PMID: 11266455
  52. Ca2+ binding site 2 in calcineurin-B modulates calmodulin-dependent calcineurin phosphatase activity.
    Biochemistry. 2001 Jul 31;40(30):8808-14 PMID: 11467941
  53. The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis.
    Dev Cell. 2001 Oct;1(4):515-25 PMID: 11703942
  54. Differential regulation of two Ca(2+) influx systems by pheromone signaling in Saccharomyces cerevisiae.
    Genetics. 2001 Dec;159(4):1527-38 PMID: 11779794
  55. Pheromone induces programmed cell death in S. cerevisiae.
    Curr Biol. 2002 Apr 2;12(7):R233-5 PMID: 11937036
  56. Mitochondrial dynamics and division in budding yeast.
    Trends Cell Biol. 2002 Apr;12(4):178-84 PMID: 11978537
  57. Merging mitochondria matters: cellular role and molecular machinery of mitochondrial fusion.
    EMBO Rep. 2002 Jun;3(6):527-31 PMID: 12052774
  58. The role of calcium-binding proteins in the control of transcription: structure to function.
    Bioessays. 2002 Jul;24(7):625-36 PMID: 12111723
  59. Apoptosis in yeast: a new model system with applications in cell biology and medicine.
    Curr Genet. 2002 Jul;41(4):208-16 PMID: 12172961
  60. In vivo site-directed mutagenesis of yeast plasmids using a three-fragment homologous recombination system.
    Biotechniques. 2002 Aug;33(2):288, 290, 292 passim PMID: 12188178
  61. Intracellular Ca2+ handling.
    Adv Exp Med Biol. 2002;513:183-96 PMID: 12575821
  62. Atypical Rho GTPases have roles in mitochondrial homeostasis and apoptosis.
    J Biol Chem. 2003 Feb 21;278(8):6495-502 PMID: 12482879
  63. Identification and functional analysis of two Ca2+-binding EF-hand motifs in the B"/PR72 subunit of protein phosphatase 2A.
    J Biol Chem. 2003 Mar 21;278(12):10697-706 PMID: 12524438
  64. A fuzzy mitochondrial fusion apparatus comes into focus.
    Nat Rev Mol Cell Biol. 2003 Jun;4(6):468-78 PMID: 12778126
  65. The tale of tail-anchored proteins: coming from the cytosol and looking for a membrane.
    J Cell Biol. 2003 Jun 23;161(6):1013-9 PMID: 12821639
  66. Staying in aerobic shape: how the structural integrity of mitochondria and mitochondrial DNA is maintained.
    Curr Opin Cell Biol. 2003 Aug;15(4):482-8 PMID: 12892790
  67. Mitochondrial membrane fusion.
    Biochim Biophys Acta. 2003 Aug 18;1641(2-3):195-202 PMID: 12914960
  68. Tim14, a novel key component of the import motor of the TIM23 protein translocase of mitochondria.
    EMBO J. 2003 Oct 1;22(19):4945-56 PMID: 14517234
  69. 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
  70. A protein complex containing Mdm10p, Mdm12p, and Mmm1p links mitochondrial membranes and DNA to the cytoskeleton-based segregation machinery.
    Mol Biol Cell. 2003 Nov;14(11):4618-27 PMID: 13679517
  71. Evidence for a two membrane-spanning autonomous mitochondrial DNA replisome.
    J Cell Biol. 2003 Nov 10;163(3):503-10 PMID: 14597773
  72. Calcium and apoptosis: facts and hypotheses.
    Oncogene. 2003 Nov 24;22(53):8619-27 PMID: 14634623
  73. A J-protein is an essential subunit of the presequence translocase-associated protein import motor of mitochondria.
    J Cell Biol. 2003 Nov 24;163(4):707-13 PMID: 14638855
  74. Mmm1p spans both the outer and inner mitochondrial membranes and contains distinct domains for targeting and foci formation.
    J Biol Chem. 2003 Dec 5;278(49):48997-9005 PMID: 12972421
  75. The division of endosymbiotic organelles.
    Science. 2003 Dec 5;302(5651):1698-704 PMID: 14657485
  76. Multiple functions of tail-anchor domains of mitochondrial outer membrane proteins.
    FEBS Lett. 2003 Dec 18;555(3):511-5 PMID: 14675765
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200405100
Published
2004-10-11
Pages
87-98
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2172521
Subset
IM
Grants
NIGMS NIH HHS · R01 GM053466 · United States
NCI NIH HHS · 5P30 CA 42014 · United States
NCRR NIH HHS · S10 RR019409-01 · United States
NIGMS NIH HHS · GM 53466 · United States
NCI NIH HHS · P30 CA042014 · United States
External Links
PubMed source DOI: 10.1083/jcb.200405100 PMC Full Text View journal details
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