Imbalanced OPA1 processing and mitochondrial fragmentation cause heart failure in mice.
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| Title: | Imbalanced OPA1 processing and mitochondrial fragmentation cause heart failure in mice. |
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| Authors: | Wai, Timothy, García-Prieto, Jaime, Baker, Michael J., Merkwirth, Carsten, Benit, Paule, Rustin, Pierre, Rupérez, Francisco Javier, Barbas, Coral, Ibañez, Borja, Langer, Thomas |
| Source: | Science (pre-March 2025). 12/4/2015, Vol. 350 Issue 6265, p1-11. 12p. |
| Subjects: | Mitochondrial proteins, Guanosine triphosphatase, Heart metabolism, Heart failure, Heart cells, Animal models in research |
| Abstract: | Mitochondrial morphology is shaped by fusion and division of their membranes. Here, we found that adult myocardial function depends on balanced mitochondrial fusion and fission, maintained by processing of the dynamin-like guanosine triphosphatase OPA1 by the mitochondrial peptidases YME1L and OMA1. Cardiac-specific ablation of Yme1l in mice activated OMA1 and accelerated OPA1 proteolysis, which triggered mitochondrial fragmentation and altered cardiac metabolism. This caused dilated cardiomyopathy and heart failure. Cardiac function and mitochondrial morphology were rescued by Oma1 deletion, which prevented OPA1 cleavage. Feeding mice a high-fat diet or ablating Yme1l in skeletal muscle restored cardiac metabolism and preserved heart function without suppressing mitochondrial fragmentation. Thus, unprocessed OPA1 is sufficient to maintain heart function, OMA1 is a critical regulator of cardiomyocyte survival, and mitochondrial morphology and cardiac metabolism are intimately linked. [ABSTRACT FROM AUTHOR] |
| Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Links: – Type: pdflink Text: Availability: 0 |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 111390930 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Imbalanced OPA1 processing and mitochondrial fragmentation cause heart failure in mice. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Wai%2C+Timothy%22">Wai, Timothy</searchLink><br /><searchLink fieldCode="AR" term="%22García-Prieto%2C+Jaime%22">García-Prieto, Jaime</searchLink><br /><searchLink fieldCode="AR" term="%22Baker%2C+Michael+J%2E%22">Baker, Michael J.</searchLink><br /><searchLink fieldCode="AR" term="%22Merkwirth%2C+Carsten%22">Merkwirth, Carsten</searchLink><br /><searchLink fieldCode="AR" term="%22Benit%2C+Paule%22">Benit, Paule</searchLink><br /><searchLink fieldCode="AR" term="%22Rustin%2C+Pierre%22">Rustin, Pierre</searchLink><br /><searchLink fieldCode="AR" term="%22Rupérez%2C+Francisco+Javier%22">Rupérez, Francisco Javier</searchLink><br /><searchLink fieldCode="AR" term="%22Barbas%2C+Coral%22">Barbas, Coral</searchLink><br /><searchLink fieldCode="AR" term="%22Ibañez%2C+Borja%22">Ibañez, Borja</searchLink><br /><searchLink fieldCode="AR" term="%22Langer%2C+Thomas%22">Langer, Thomas</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 12/4/2015, Vol. 350 Issue 6265, p1-11. 12p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Mitochondrial+proteins%22">Mitochondrial proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Guanosine+triphosphatase%22">Guanosine triphosphatase</searchLink><br /><searchLink fieldCode="DE" term="%22Heart+metabolism%22">Heart metabolism</searchLink><br /><searchLink fieldCode="DE" term="%22Heart+failure%22">Heart failure</searchLink><br /><searchLink fieldCode="DE" term="%22Heart+cells%22">Heart cells</searchLink><br /><searchLink fieldCode="DE" term="%22Animal+models+in+research%22">Animal models in research</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Mitochondrial morphology is shaped by fusion and division of their membranes. Here, we found that adult myocardial function depends on balanced mitochondrial fusion and fission, maintained by processing of the dynamin-like guanosine triphosphatase OPA1 by the mitochondrial peptidases YME1L and OMA1. Cardiac-specific ablation of Yme1l in mice activated OMA1 and accelerated OPA1 proteolysis, which triggered mitochondrial fragmentation and altered cardiac metabolism. This caused dilated cardiomyopathy and heart failure. Cardiac function and mitochondrial morphology were rescued by Oma1 deletion, which prevented OPA1 cleavage. Feeding mice a high-fat diet or ablating Yme1l in skeletal muscle restored cardiac metabolism and preserved heart function without suppressing mitochondrial fragmentation. Thus, unprocessed OPA1 is sufficient to maintain heart function, OMA1 is a critical regulator of cardiomyocyte survival, and mitochondrial morphology and cardiac metabolism are intimately linked. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
| PLink | https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=111390930 |
| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1126/science.aad0116 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 12 StartPage: 1 Subjects: – SubjectFull: Mitochondrial proteins Type: general – SubjectFull: Guanosine triphosphatase Type: general – SubjectFull: Heart metabolism Type: general – SubjectFull: Heart failure Type: general – SubjectFull: Heart cells Type: general – SubjectFull: Animal models in research Type: general Titles: – TitleFull: Imbalanced OPA1 processing and mitochondrial fragmentation cause heart failure in mice. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Wai, Timothy – PersonEntity: Name: NameFull: García-Prieto, Jaime – PersonEntity: Name: NameFull: Baker, Michael J. – PersonEntity: Name: NameFull: Merkwirth, Carsten – PersonEntity: Name: NameFull: Benit, Paule – PersonEntity: Name: NameFull: Rustin, Pierre – PersonEntity: Name: NameFull: Rupérez, Francisco Javier – PersonEntity: Name: NameFull: Barbas, Coral – PersonEntity: Name: NameFull: Ibañez, Borja – PersonEntity: Name: NameFull: Langer, Thomas IsPartOfRelationships: – BibEntity: Dates: – D: 04 M: 12 Text: 12/4/2015 Type: published Y: 2015 Identifiers: – Type: issn-print Value: 00368075 Numbering: – Type: volume Value: 350 – Type: issue Value: 6265 Titles: – TitleFull: Science (pre-March 2025) Type: main |
| ResultId | 1 |
