Cargando…

Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane

Mitochondrial membrane dynamics is a cellular rheostat that relates metabolic function and organelle morphology. Using an in vitro reconstitution system, we describe a mechanism for how mitochondrial inner-membrane fusion is regulated by the ratio of two forms of Opa1. We found that the long-form of...

Descripción completa

Detalles Bibliográficos
Autores principales: Ge, Yifan, Shi, Xiaojun, Boopathy, Sivakumar, McDonald, Julie, Smith, Adam W, Chao, Luke H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299343/
https://www.ncbi.nlm.nih.gov/pubmed/31922487
http://dx.doi.org/10.7554/eLife.50973
_version_ 1783547367061979136
author Ge, Yifan
Shi, Xiaojun
Boopathy, Sivakumar
McDonald, Julie
Smith, Adam W
Chao, Luke H
author_facet Ge, Yifan
Shi, Xiaojun
Boopathy, Sivakumar
McDonald, Julie
Smith, Adam W
Chao, Luke H
author_sort Ge, Yifan
collection PubMed
description Mitochondrial membrane dynamics is a cellular rheostat that relates metabolic function and organelle morphology. Using an in vitro reconstitution system, we describe a mechanism for how mitochondrial inner-membrane fusion is regulated by the ratio of two forms of Opa1. We found that the long-form of Opa1 (l-Opa1) is sufficient for membrane docking, hemifusion and low levels of content release. However, stoichiometric levels of the processed, short form of Opa1 (s-Opa1) work together with l-Opa1 to mediate efficient and fast membrane pore opening. Additionally, we found that excess levels of s-Opa1 inhibit fusion activity, as seen under conditions of altered proteostasis. These observations describe a mechanism for gating membrane fusion.
format Online
Article
Text
id pubmed-7299343
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-72993432020-06-18 Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane Ge, Yifan Shi, Xiaojun Boopathy, Sivakumar McDonald, Julie Smith, Adam W Chao, Luke H eLife Structural Biology and Molecular Biophysics Mitochondrial membrane dynamics is a cellular rheostat that relates metabolic function and organelle morphology. Using an in vitro reconstitution system, we describe a mechanism for how mitochondrial inner-membrane fusion is regulated by the ratio of two forms of Opa1. We found that the long-form of Opa1 (l-Opa1) is sufficient for membrane docking, hemifusion and low levels of content release. However, stoichiometric levels of the processed, short form of Opa1 (s-Opa1) work together with l-Opa1 to mediate efficient and fast membrane pore opening. Additionally, we found that excess levels of s-Opa1 inhibit fusion activity, as seen under conditions of altered proteostasis. These observations describe a mechanism for gating membrane fusion. eLife Sciences Publications, Ltd 2020-01-10 /pmc/articles/PMC7299343/ /pubmed/31922487 http://dx.doi.org/10.7554/eLife.50973 Text en © 2020, Ge et al http://creativecommons.org/licenses/by/4.0/ 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 Structural Biology and Molecular Biophysics
Ge, Yifan
Shi, Xiaojun
Boopathy, Sivakumar
McDonald, Julie
Smith, Adam W
Chao, Luke H
Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane
title Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane
title_full Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane
title_fullStr Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane
title_full_unstemmed Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane
title_short Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane
title_sort two forms of opa1 cooperate to complete fusion of the mitochondrial inner-membrane
topic Structural Biology and Molecular Biophysics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299343/
https://www.ncbi.nlm.nih.gov/pubmed/31922487
http://dx.doi.org/10.7554/eLife.50973
work_keys_str_mv AT geyifan twoformsofopa1cooperatetocompletefusionofthemitochondrialinnermembrane
AT shixiaojun twoformsofopa1cooperatetocompletefusionofthemitochondrialinnermembrane
AT boopathysivakumar twoformsofopa1cooperatetocompletefusionofthemitochondrialinnermembrane
AT mcdonaldjulie twoformsofopa1cooperatetocompletefusionofthemitochondrialinnermembrane
AT smithadamw twoformsofopa1cooperatetocompletefusionofthemitochondrialinnermembrane
AT chaolukeh twoformsofopa1cooperatetocompletefusionofthemitochondrialinnermembrane