The OPA1-dependent mitochondrial cristae remodeling pathway controls atrophic, apoptotic, and ischemic tissue damage

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 t...

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Detalles Bibliográficos
Autores: Varanita, Tatiana, Soriano, Maria Eugenia, Romanello, Vanina, Zaglia, Tania, Quintana-Cabrera, Rubén, Semenzato, Martina, Menabò, Roberta, Costa, Veronica, Civiletto, Gabriele, Pesce, Paola, Viscomi, Carlo, Zeviani, Massimo, Di Lisa, Fabio, Mongillo, Marco, Sandri, Marco, Scorrano, Luca
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/415184
Acceso en línea:http://hdl.handle.net/10261/415184
https://api.elsevier.com/content/abstract/scopus_id/84930607266
Access Level:acceso abierto
Palabra clave:http://metadata.un.org/sdg/3
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Descripción
Sumario: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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