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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/50973 |
| _version_ | 1818026830530084864 |
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| author | Yifan Ge Xiaojun Shi Sivakumar Boopathy Julie McDonald Adam W Smith Luke H Chao |
| author_facet | Yifan Ge Xiaojun Shi Sivakumar Boopathy Julie McDonald Adam W Smith Luke H Chao |
| author_sort | Yifan Ge |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-10T04:38:14Z |
| format | Article |
| id | doaj.art-25fe04680a2e4468befc5c839b43b4d7 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T04:38:14Z |
| publishDate | 2020-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-25fe04680a2e4468befc5c839b43b4d72022-12-22T02:01:56ZengeLife Sciences Publications LtdeLife2050-084X2020-01-01910.7554/eLife.50973Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membraneYifan Ge0https://orcid.org/0000-0001-9135-9569Xiaojun Shi1https://orcid.org/0000-0002-8060-5880Sivakumar Boopathy2https://orcid.org/0000-0003-0524-3338Julie McDonald3https://orcid.org/0000-0002-3715-9619Adam W Smith4https://orcid.org/0000-0001-5216-9017Luke H Chao5https://orcid.org/0000-0002-4849-4148Department of Molecular Biology, Massachusetts General Hospital, Boston, United StatesDepartment of Chemistry, University of Akron, Akron, United StatesDepartment of Molecular Biology, Massachusetts General Hospital, Boston, United StatesDepartment of Molecular Biology, Massachusetts General Hospital, Boston, United StatesDepartment of Chemistry, University of Akron, Akron, United StatesDepartment of Molecular Biology, Massachusetts General Hospital, Boston, United States; Department of Genetics, Harvard Medical School, Boston, United StatesMitochondrial 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.https://elifesciences.org/articles/50973membranesin vitro reconstitutionfusionmitochondria |
| spellingShingle | Yifan Ge Xiaojun Shi Sivakumar Boopathy Julie McDonald Adam W Smith Luke H Chao Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane eLife membranes in vitro reconstitution fusion mitochondria |
| 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 | membranes in vitro reconstitution fusion mitochondria |
| url | https://elifesciences.org/articles/50973 |
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