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Identification of new OPA1 cleavage site reveals that short isoforms regulate mitochondrial fusion
OPA1, a large GTPase of the dynamin superfamily, mediates fusion of the mitochondrial inner membranes, regulates cristae morphology, and maintains respiratory chain function. Inner membrane–anchored long forms of OPA1 (l-OPA1) are proteolytically processed by the OMA1 or YME1L proteases, acting at c...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120690/ https://www.ncbi.nlm.nih.gov/pubmed/33237841 http://dx.doi.org/10.1091/mbc.E20-09-0605 |
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author | Wang, Ruohan Mishra, Prashant Garbis, Spiros D. Moradian, Annie Sweredoski, Michael J. Chan, David C. |
author_facet | Wang, Ruohan Mishra, Prashant Garbis, Spiros D. Moradian, Annie Sweredoski, Michael J. Chan, David C. |
author_sort | Wang, Ruohan |
collection | PubMed |
description | OPA1, a large GTPase of the dynamin superfamily, mediates fusion of the mitochondrial inner membranes, regulates cristae morphology, and maintains respiratory chain function. Inner membrane–anchored long forms of OPA1 (l-OPA1) are proteolytically processed by the OMA1 or YME1L proteases, acting at cleavage sites S1 and S2, respectively, to produce short forms (s-OPA1). In both mice and humans, half of the mRNA splice forms of Opa1 are constitutively processed to yield exclusively s-OPA1. However, the function of s-OPA1 in mitochondrial fusion has been debated, because in some stress conditions, s-OPA1 is dispensable for fusion. By constructing cells in which the Opa1 locus no longer produces transcripts with S2 cleavage sites, we generated a simplified system to identify the new YME1L-dependent site S3 that mediates constitutive and complete cleavage of OPA1. We show that mitochondrial morphology is highly sensitive to the ratio of l-OPA1 to s-OPA1, indicating that s-OPA1 regulates mitochondrial fusion. |
format | Online Article Text |
id | pubmed-8120690 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-81206902021-05-14 Identification of new OPA1 cleavage site reveals that short isoforms regulate mitochondrial fusion Wang, Ruohan Mishra, Prashant Garbis, Spiros D. Moradian, Annie Sweredoski, Michael J. Chan, David C. Mol Biol Cell Articles OPA1, a large GTPase of the dynamin superfamily, mediates fusion of the mitochondrial inner membranes, regulates cristae morphology, and maintains respiratory chain function. Inner membrane–anchored long forms of OPA1 (l-OPA1) are proteolytically processed by the OMA1 or YME1L proteases, acting at cleavage sites S1 and S2, respectively, to produce short forms (s-OPA1). In both mice and humans, half of the mRNA splice forms of Opa1 are constitutively processed to yield exclusively s-OPA1. However, the function of s-OPA1 in mitochondrial fusion has been debated, because in some stress conditions, s-OPA1 is dispensable for fusion. By constructing cells in which the Opa1 locus no longer produces transcripts with S2 cleavage sites, we generated a simplified system to identify the new YME1L-dependent site S3 that mediates constitutive and complete cleavage of OPA1. We show that mitochondrial morphology is highly sensitive to the ratio of l-OPA1 to s-OPA1, indicating that s-OPA1 regulates mitochondrial fusion. The American Society for Cell Biology 2021-01-15 /pmc/articles/PMC8120690/ /pubmed/33237841 http://dx.doi.org/10.1091/mbc.E20-09-0605 Text en © 2021 Wang et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. https://creativecommons.org/licenses/by-nc-sa/3.0/This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License. |
spellingShingle | Articles Wang, Ruohan Mishra, Prashant Garbis, Spiros D. Moradian, Annie Sweredoski, Michael J. Chan, David C. Identification of new OPA1 cleavage site reveals that short isoforms regulate mitochondrial fusion |
title | Identification of new OPA1 cleavage site reveals that short isoforms regulate mitochondrial fusion |
title_full | Identification of new OPA1 cleavage site reveals that short isoforms regulate mitochondrial fusion |
title_fullStr | Identification of new OPA1 cleavage site reveals that short isoforms regulate mitochondrial fusion |
title_full_unstemmed | Identification of new OPA1 cleavage site reveals that short isoforms regulate mitochondrial fusion |
title_short | Identification of new OPA1 cleavage site reveals that short isoforms regulate mitochondrial fusion |
title_sort | identification of new opa1 cleavage site reveals that short isoforms regulate mitochondrial fusion |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120690/ https://www.ncbi.nlm.nih.gov/pubmed/33237841 http://dx.doi.org/10.1091/mbc.E20-09-0605 |
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