Universität zu Köln

Wai, Timothy ORCID: 0000-0002-6770-6222, Garcia-Prieto, Jaime, Baker, Michael J., Merkwirth, Carsten ORCID: 0000-0001-8895-3495, Benit, Paule, Rustin, Pierre, Javier Ruperez, Francisco, Barbas, Coral ORCID: 0000-0003-4722-491X, Ibanez, Borja ORCID: 0000-0002-5036-254X and Langer, Thomas ORCID: 0000-0003-1250-1462 (2015). Imbalanced OPA1 processing and mitochondrial fragmentation cause heart failure in mice. Science, 350 (6265). WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 1095-9203

Full text not available from this repository.

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wai, Timothy UNSPECIFIED orcid.org/0000-0002-6770-6222 UNSPECIFIED Garcia-Prieto, Jaime UNSPECIFIED UNSPECIFIED UNSPECIFIED Baker, Michael J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkwirth, Carsten UNSPECIFIED orcid.org/0000-0001-8895-3495 UNSPECIFIED Benit, Paule UNSPECIFIED UNSPECIFIED UNSPECIFIED Rustin, Pierre UNSPECIFIED UNSPECIFIED UNSPECIFIED Javier Ruperez, Francisco UNSPECIFIED UNSPECIFIED UNSPECIFIED Barbas, Coral UNSPECIFIED orcid.org/0000-0003-4722-491X UNSPECIFIED Ibanez, Borja UNSPECIFIED orcid.org/0000-0002-5036-254X UNSPECIFIED Langer, Thomas UNSPECIFIED orcid.org/0000-0003-1250-1462 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-383920
DOI:	10.1126/science.aad0116
Journal or Publication Title:	Science
Volume:	350
Number:	6265
Date:	2015
Publisher:	AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication:	WASHINGTON
ISSN:	1095-9203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CYTOCHROME-C RELEASE; DIET-INDUCED OBESITY; PROTEOLYTIC CLEAVAGE; SKELETAL-MUSCLE; PROTEASE OMA1; MOUSE HEARTS; GLUCOSE-HOMEOSTASIS; MITOFUSIN 2; FUSION; METABOLISM Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/38392