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MIEF1/2 orchestrate mitochondrial dynamics through direct engagement with both the fission and fusion machineries
BACKGROUND: Mitochondrial dynamics is the result of a dynamic balance between fusion and fission events, which are driven via a set of mitochondria-shaping proteins. These proteins are generally considered to be binary components of either the fission or fusion machinery, but potential crosstalk bet...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8532385/ https://www.ncbi.nlm.nih.gov/pubmed/34674699 http://dx.doi.org/10.1186/s12915-021-01161-7 |
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author | Yu, Rong Liu, Tong Jin, Shao-Bo Ankarcrona, Maria Lendahl, Urban Nistér, Monica Zhao, Jian |
author_facet | Yu, Rong Liu, Tong Jin, Shao-Bo Ankarcrona, Maria Lendahl, Urban Nistér, Monica Zhao, Jian |
author_sort | Yu, Rong |
collection | PubMed |
description | BACKGROUND: Mitochondrial dynamics is the result of a dynamic balance between fusion and fission events, which are driven via a set of mitochondria-shaping proteins. These proteins are generally considered to be binary components of either the fission or fusion machinery, but potential crosstalk between the fission and fusion machineries remains less explored. In the present work, we analyzed the roles of mitochondrial elongation factors 1 and 2 (MIEF1/2), core components of the fission machinery in mammals. RESULTS: We show that MIEFs (MIEF1/2), besides their action in the fission machinery, regulate mitochondrial fusion through direct interaction with the fusion proteins Mfn1 and Mfn2, suggesting that MIEFs participate in not only fission but also fusion. Elevated levels of MIEFs enhance mitochondrial fusion in an Mfn1/2- and OPA1-dependent but Drp1-independent manner. Moreover, mitochondrial localization and self-association of MIEFs are crucial for their fusion-promoting ability. In addition, we show that MIEF1/2 can competitively decrease the interaction of hFis1 with Mfn1 and Mfn2, alleviating hFis1-induced mitochondrial fragmentation and contributing to mitochondrial fusion. CONCLUSIONS: Our study suggests that MIEFs serve as a central hub that interacts with and regulates both the fission and fusion machineries, which uncovers a novel mechanism for balancing these opposing forces of mitochondrial dynamics in mammals. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12915-021-01161-7. |
format | Online Article Text |
id | pubmed-8532385 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-85323852021-10-25 MIEF1/2 orchestrate mitochondrial dynamics through direct engagement with both the fission and fusion machineries Yu, Rong Liu, Tong Jin, Shao-Bo Ankarcrona, Maria Lendahl, Urban Nistér, Monica Zhao, Jian BMC Biol Research Article BACKGROUND: Mitochondrial dynamics is the result of a dynamic balance between fusion and fission events, which are driven via a set of mitochondria-shaping proteins. These proteins are generally considered to be binary components of either the fission or fusion machinery, but potential crosstalk between the fission and fusion machineries remains less explored. In the present work, we analyzed the roles of mitochondrial elongation factors 1 and 2 (MIEF1/2), core components of the fission machinery in mammals. RESULTS: We show that MIEFs (MIEF1/2), besides their action in the fission machinery, regulate mitochondrial fusion through direct interaction with the fusion proteins Mfn1 and Mfn2, suggesting that MIEFs participate in not only fission but also fusion. Elevated levels of MIEFs enhance mitochondrial fusion in an Mfn1/2- and OPA1-dependent but Drp1-independent manner. Moreover, mitochondrial localization and self-association of MIEFs are crucial for their fusion-promoting ability. In addition, we show that MIEF1/2 can competitively decrease the interaction of hFis1 with Mfn1 and Mfn2, alleviating hFis1-induced mitochondrial fragmentation and contributing to mitochondrial fusion. CONCLUSIONS: Our study suggests that MIEFs serve as a central hub that interacts with and regulates both the fission and fusion machineries, which uncovers a novel mechanism for balancing these opposing forces of mitochondrial dynamics in mammals. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12915-021-01161-7. BioMed Central 2021-10-21 /pmc/articles/PMC8532385/ /pubmed/34674699 http://dx.doi.org/10.1186/s12915-021-01161-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Yu, Rong Liu, Tong Jin, Shao-Bo Ankarcrona, Maria Lendahl, Urban Nistér, Monica Zhao, Jian MIEF1/2 orchestrate mitochondrial dynamics through direct engagement with both the fission and fusion machineries |
title | MIEF1/2 orchestrate mitochondrial dynamics through direct engagement with both the fission and fusion machineries |
title_full | MIEF1/2 orchestrate mitochondrial dynamics through direct engagement with both the fission and fusion machineries |
title_fullStr | MIEF1/2 orchestrate mitochondrial dynamics through direct engagement with both the fission and fusion machineries |
title_full_unstemmed | MIEF1/2 orchestrate mitochondrial dynamics through direct engagement with both the fission and fusion machineries |
title_short | MIEF1/2 orchestrate mitochondrial dynamics through direct engagement with both the fission and fusion machineries |
title_sort | mief1/2 orchestrate mitochondrial dynamics through direct engagement with both the fission and fusion machineries |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8532385/ https://www.ncbi.nlm.nih.gov/pubmed/34674699 http://dx.doi.org/10.1186/s12915-021-01161-7 |
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