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

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 ele...

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Autores principales: Brandt, Tobias, Cavellini, Laetitia, Kühlbrandt, Werner, Cohen, Mickaël M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929004/
https://www.ncbi.nlm.nih.gov/pubmed/27253069
http://dx.doi.org/10.7554/eLife.14618
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author Brandt, Tobias
Cavellini, Laetitia
Kühlbrandt, Werner
Cohen, Mickaël M
author_facet Brandt, Tobias
Cavellini, Laetitia
Kühlbrandt, Werner
Cohen, Mickaël M
author_sort Brandt, Tobias
collection PubMed
description 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. DOI: http://dx.doi.org/10.7554/eLife.14618.001
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spelling pubmed-49290042016-07-05 A mitofusin-dependent docking ring complex triggers mitochondrial fusion in vitro Brandt, Tobias Cavellini, Laetitia Kühlbrandt, Werner Cohen, Mickaël M eLife Biophysics and Structural Biology 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. DOI: http://dx.doi.org/10.7554/eLife.14618.001 eLife Sciences Publications, Ltd 2016-06-02 /pmc/articles/PMC4929004/ /pubmed/27253069 http://dx.doi.org/10.7554/eLife.14618 Text en © 2016, Brandt et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biophysics and Structural Biology
Brandt, Tobias
Cavellini, Laetitia
Kühlbrandt, Werner
Cohen, Mickaël M
A mitofusin-dependent docking ring complex triggers mitochondrial fusion in vitro
title A mitofusin-dependent docking ring complex triggers mitochondrial fusion in vitro
title_full A mitofusin-dependent docking ring complex triggers mitochondrial fusion in vitro
title_fullStr A mitofusin-dependent docking ring complex triggers mitochondrial fusion in vitro
title_full_unstemmed A mitofusin-dependent docking ring complex triggers mitochondrial fusion in vitro
title_short A mitofusin-dependent docking ring complex triggers mitochondrial fusion in vitro
title_sort mitofusin-dependent docking ring complex triggers mitochondrial fusion in vitro
topic Biophysics and Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929004/
https://www.ncbi.nlm.nih.gov/pubmed/27253069
http://dx.doi.org/10.7554/eLife.14618
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