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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Main Authors: Tobias Brandt, Laetitia Cavellini, Werner Kühlbrandt, Mickaël M Cohen
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2016-06-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/14618
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author Tobias Brandt
Laetitia Cavellini
Werner Kühlbrandt
Mickaël M Cohen
author_facet Tobias Brandt
Laetitia Cavellini
Werner Kühlbrandt
Mickaël M Cohen
author_sort Tobias Brandt
collection DOAJ
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.
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spelling doaj.art-6e6ed8bf146c451d9972f4d84f2e61cc2022-12-22T04:32:37ZengeLife Sciences Publications LtdeLife2050-084X2016-06-01510.7554/eLife.14618A mitofusin-dependent docking ring complex triggers mitochondrial fusion in vitroTobias Brandt0Laetitia Cavellini1Werner Kühlbrandt2Mickaël M Cohen3https://orcid.org/0000-0002-1372-680XMax Planck Institute of Biophysics, Frankfurt, GermanyLaboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes, Institut de Biologie Physico-Chimique, Sorbonne Universités, Paris, FranceMax Planck Institute of Biophysics, Frankfurt, GermanyLaboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes, Institut de Biologie Physico-Chimique, Sorbonne Universités, Paris, FranceFusion 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.https://elifesciences.org/articles/14618mitochondriamembrane fusionmitofusindynamin-related-proteinsmitochondrial dynamicscryo-EM
spellingShingle Tobias Brandt
Laetitia Cavellini
Werner Kühlbrandt
Mickaël M Cohen
A mitofusin-dependent docking ring complex triggers mitochondrial fusion in vitro
eLife
mitochondria
membrane fusion
mitofusin
dynamin-related-proteins
mitochondrial dynamics
cryo-EM
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 mitochondria
membrane fusion
mitofusin
dynamin-related-proteins
mitochondrial dynamics
cryo-EM
url https://elifesciences.org/articles/14618
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