TY - JOUR
T1 - The Opa1-dependent mitochondrial cristae remodeling pathway controls atrophic, apoptotic, and ischemic tissue damage
AU - Varanita, Tatiana
AU - Soriano, Maria Eugenia
AU - Romanello, Vanina
AU - Zaglia, Tania
AU - Quintana-Cabrera, Rubén
AU - Semenzato, Martina
AU - Menabò, Roberta
AU - Costa, Veronica
AU - Civiletto, Gabriele
AU - Pesce, Paola
AU - Viscomi, Carlo
AU - Zeviani, Massimo
AU - Di Lisa, Fabio
AU - Mongillo, Marco
AU - Sandri, Marco
AU - Scorrano, Luca
PY - 2015/6/2
Y1 - 2015/6/2
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cmet.2015.05.007
DO - 10.1016/j.cmet.2015.05.007
M3 - Article
AN - SCOPUS:84930607266
VL - 21
SP - 834
EP - 844
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 6
ER -