2015/06/01 by Tatiana Varanita, María Eugenia Soriano, Vanina Romanello +13 · 462 citations
Biochemistry, Genetics and Molecular Biology · #Mitochondrial Function and Pathology #ATP Synthase and ATPases Research #Metabolism and Genetic Disorders #Apoptosis #Mitochondrion #Cell biology #Biology #Biochemistry
paper · pdf · doi:10.1016/j.cmet.2015.05.007
published in Cell Metabolism 21(6), 834-844 (Cell Press)
openalex publication_date 2015/06/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/29
Mitochondrial morphological and ultrastructural changes occur during apoptosis and autophagy, but whether they are relevant in vivo for tissue response to damage is unclear. Here we investigate the role of the optic atrophy 1 (OPA1)-dependent cristae remodeling pathway in vivo and provide evidence that it regulates the response of multiple tissues to apoptotic, necrotic, and atrophic stimuli. Genetic inhibition of the cristae remodeling pathway in vivo does not affect development, but protects mice from denervation-induced muscular atrophy, ischemic heart and brain damage, as well as hepatocellular apoptosis. Mechanistically, OPA1-dependent mitochondrial cristae stabilization increases mitochondrial respiratory efficiency and blunts mitochondrial dysfunction, cytochrome c release, and reactive oxygen species production. Our results indicate that the OPA1-dependent cristae remodeling pathway is a fundamental, targetable determinant of tissue damage in vivo.