A mitofusin-dependent docking ring complex triggers mitochondrial fusion in vitro

被引:89
作者
Brandt, Tobias [1 ]
Cavellini, Laetitia [2 ]
Kuehlbrandt, Werner [1 ]
Cohen, Mickael M. [2 ]
机构
[1] Max Planck Inst Biophys, Frankfurt, Germany
[2] Univ Paris 04, Inst Biol Physicochim, Lab Biol Mol & Cellulaire Eucaryotes, Paris, France
关键词
INNER-MEMBRANE-FUSION; DYNAMIN-LIKE PROTEIN; SACCHAROMYCES-CEREVISIAE; STRUCTURAL BASIS; REQUIRES; YEAST; ATLASTIN; GTP; DOMAIN; OUTER;
D O I
10.7554/eLife.14618
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Fusion of mitochondrial outer membranes is crucial for proper organelle function and involves large GTPases called mitofusins. The discrete steps that allow mitochondria to attach to one another and merge their outer membranes are unknown. By combining an in vitro mitochondrial fusion assay with electron cryo-tomography (cryo-ET), we visualize the junction between attached mitochondria isolated from Saccharomyces cerevisiae and observe complexes that mediate this attachment. We find that cycles of GTP hydrolysis induce progressive formation of a docking ring structure around extended areas of contact. Further GTP hydrolysis triggers local outer membrane fusion at the periphery of the contact region. These findings unravel key features of mitofusin-dependent fusion of outer membranes and constitute an important advance in our understanding of how mitochondria connect and merge.
引用
收藏
页数:23
相关论文
共 50 条
[1]   Membrane Tethering and Nucleotide-dependent Conformational Changes Drive Mitochondrial Genome Maintenance (Mgm1) Protein-mediated Membrane Fusion [J].
Abutbul-Ionita, Inbal ;
Rujiviphat, Jarungjit ;
Nir, Iftach ;
McQuibban, G. Angus ;
Danino, Dganit .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (44) :36634-36638
[2]   A Mutation Associated with CMT2A Neuropathy Causes Defects in Fzo1 GTP Hydrolysis, Ubiquitylation, and Protein Turnover [J].
Amiott, Elizabeth A. ;
Cohen, Mickael M. ;
Saint-Georges, Yann ;
Weissman, Allan M. ;
Shaw, Janet M. .
MOLECULAR BIOLOGY OF THE CELL, 2009, 20 (23) :5026-5035
[3]   Ugo1 and Mdm30 act sequentially during Fzo1-mediated mitochondrial outer membrane fusion [J].
Anton, Fabian ;
Fres, Julia M. ;
Schauss, Astrid ;
Pinson, Benoit ;
Praefcke, Gerrit J. K. ;
Langer, Thomas ;
Escobar-Henriques, Mafalda .
JOURNAL OF CELL SCIENCE, 2011, 124 (07) :1126-1135
[4]   A minimal peptide substrate in biotin holoenzyme synthetase-catalyzed biotinylation [J].
Beckett, D ;
Kovaleva, E ;
Schatz, PJ .
PROTEIN SCIENCE, 1999, 8 (04) :921-929
[5]   Structures of the atlastin GTPase provide insight into homotypic fusion of endoplasmic reticulum membranes [J].
Bian, Xin ;
Klemm, Robin W. ;
Liu, Tina Y. ;
Zhang, Miao ;
Sun, Sha ;
Sui, Xuewu ;
Liu, Xinqi ;
Rapoport, Tom A. ;
Hu, Junjie .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (10) :3976-3981
[6]   Dynamin Assembly Strategies and Adaptor Review Proteins in Mitochondrial Fission [J].
Bui, Huyen T. ;
Shaw, Janet M. .
CURRENT BIOLOGY, 2013, 23 (19) :R891-R899
[7]   Structural basis for conformational switching and GTP loading of the large G protein atlastin [J].
Byrnes, Laura J. ;
Singh, Avtar ;
Szeto, Kylan ;
Benvin, Nicole M. ;
O'Donnell, John P. ;
Zipfel, Warren R. ;
Sondermann, Holger .
EMBO JOURNAL, 2013, 32 (03) :369-384
[8]   Coats, tethers, Rabs, and SNAREs work together to mediate the intracellular destination of a transport vesicle [J].
Cai, Huaqing ;
Reinisch, Karin ;
Ferro-Novick, Susan .
DEVELOPMENTAL CELL, 2007, 12 (05) :671-682
[9]   Sequential requirements for the GTPase domain of the mitofusin Fzo1 and the ubiquitin ligase SCFMdm30 in mitochondrial outer membrane fusion [J].
Cohen, Mickael M. ;
Amiott, Elizabeth A. ;
Day, Adam R. ;
Leboucher, Guillaume P. ;
Pryce, Erin N. ;
Glickman, Michael H. ;
McCaffery, J. Michael ;
Shaw, Janet M. ;
Weissman, Allan M. .
JOURNAL OF CELL SCIENCE, 2011, 124 (09) :1403-1410
[10]   Ubiquitin-proteasome-dependent degradation of a mitofusin, a critical regulator of mitochondrial fusion [J].
Cohen, Mickael M. J. ;
Leboucher, Guillaume P. ;
Livnat-Levanon, Nurit ;
Glickman, Michael H. ;
Weissman, Allan M. .
MOLECULAR BIOLOGY OF THE CELL, 2008, 19 (06) :2457-2464