The Opa1-dependent mitochondrial cristae remodeling pathway controls atrophic, apoptotic, and ischemic tissue damage

Tatiana Varanita, Maria Eugenia Soriano, Vanina Romanello, Tania Zaglia, Rubén Quintana-Cabrera, Martina Semenzato, Roberta Menabò, Veronica Costa, Gabriele Civiletto, Paola Pesce, Carlo Viscomi, Massimo Zeviani, Fabio Di Lisa, Marco Mongillo, Marco Sandri, Luca Scorrano

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)834-844
Number of pages11
JournalCell Metabolism
Volume21
Issue number6
DOIs
Publication statusPublished - Jun 2 2015

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

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