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

TitleThe OPA1-dependent mitochondrial cristae remodeling pathway controls atrophic, apoptotic, and ischemic tissue damage.
Publication TypeJournal Article
Year of Publication2015
AuthorsVaranita, T, Soriano, MEugenia, Romanello, V, Zaglia, T, Quintana-Cabrera, R, Semenzato, M, Menabò, R, Costa, V, Civiletto, G, Pesce, P, Viscomi, C, Zeviani, M, Di Lisa, F, Mongillo, M, Sandri, M, Scorrano, L
JournalCell Metab
Volume21
Issue6
Pagination834-44
Date Published2015 Jun 2
ISSN1932-7420
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.

DOI10.1016/j.cmet.2015.05.007
Alternate JournalCell Metab.
Citation Key10.1016/j.cmet.2015.05.007
PubMed ID26039448
PubMed Central IDPMC4457892
Grant ListMC_UP_1002/1 / / Medical Research Council / United Kingdom