线粒体融合
线粒体
线粒体分裂
心力衰竭
心功能曲线
细胞生物学
生物
内科学
骨骼肌
内分泌学
线粒体DNA
医学
生物化学
基因
作者
Timothy Wai,Jaime García‐Prieto,Michael J. Baker,Carsten Merkwirth,Paule Bénit,Pierre Rustin,Javier Rupérez,Coral Barbas,Borja Ibáñez,Thomas Langer
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2015-12-04
卷期号:350 (6265)
被引量:398
标识
DOI:10.1126/science.aad0116
摘要
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.
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