Imbalanced OPA1 processing and mitochondrial fragmentation cause heart failure in mice

• DOI: 10.1126/science.aad0116
• Publication Date: 2015-12-03T19:28:26Z
• Authors: Timothy Wai; Jaime García-Prieto; Michael J. Baker; Carsten Merkwirth; Paule Benit; Pierre Rustin; Francisco Javier ...; Coral Barbas; Borja Ibañez; Thomas Langer
• Keywords: Fragmentation

Mitochondrial morphology is shaped by fusion and division of their membranes. Here, we found that adult myocardial function depends on balanced mitochondrial fission, maintained processing the dynamin-like guanosine triphosphatase OPA1 peptidases YME1L OMA1. Cardiac-specific ablation Yme1l in mice activated OMA1 accelerated proteolysis, which triggered fragmentation altered cardiac metabolism. This caused dilated cardiomyopathy heart failure. Cardiac were rescued Oma1 deletion, prevented cleavage. Feeding a high-fat diet or ablating skeletal muscle restored metabolism preserved without suppressing fragmentation. Thus, unprocessed sufficient to maintain function, critical regulator cardiomyocyte survival, are intimately linked.