title: The OPA1-dependent mitochondrial cristae remodeling pathway controls atrophic, apoptotic, and ischemic tissue damage.
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.
authors.affiliation: Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy; Department of Biology, University of Padova, Via C. Colombo 3, 35121 Padova, Italy.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Varanita
authors.affiliation: Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy; Department of Biology, University of Padova, Via C. Colombo 3, 35121 Padova, Italy.
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Soriano
authors.affiliation: Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy; Department of Biomedical Sciences, University of Padova, Via C. Colombo 3, 35121 Padova, Italy.
authors.forename: Vanina
authors.initials: V
authors.lastname: Romanello
authors.affiliation: Department of Biomedical Sciences, University of Padova, Via C. Colombo 3, 35121 Padova, Italy.
authors.forename: Tania
authors.initials: T
authors.lastname: Zaglia
authors.affiliation: Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy; Department of Biology, University of Padova, Via C. Colombo 3, 35121 Padova, Italy.
authors.forename: Rubén
authors.initials: R
authors.lastname: Quintana-Cabrera
authors.affiliation: Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy; Department of Biology, University of Padova, Via C. Colombo 3, 35121 Padova, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Semenzato
authors.affiliation: Institute of Neuroscience, National Research Council of Italy (CNR), Via C. Colombo 3, 35121 Padova, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Menabò
authors.affiliation: Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Costa
authors.affiliation: Fondazione IRCCS Istituto Neurologico "C. Besta," Via L. Temolo 4, 20126 Milan, Italy; MRC Mitochondrial Biology Unit, MRC Building, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Civiletto
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Pesce
authors.affiliation: Fondazione IRCCS Istituto Neurologico "C. Besta," Via L. Temolo 4, 20126 Milan, Italy; MRC Mitochondrial Biology Unit, MRC Building, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Carlo
authors.initials: C
authors.lastname: Viscomi
authors.affiliation: Fondazione IRCCS Istituto Neurologico "C. Besta," Via L. Temolo 4, 20126 Milan, Italy; MRC Mitochondrial Biology Unit, MRC Building, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Massimo
authors.initials: M
authors.lastname: Zeviani
authors.affiliation: Department of Biomedical Sciences, University of Padova, Via C. Colombo 3, 35121 Padova, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Lisa
authors.affiliation: Department of Biomedical Sciences, University of Padova, Via C. Colombo 3, 35121 Padova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Mongillo
authors.affiliation: Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy; Department of Biomedical Sciences, University of Padova, Via C. Colombo 3, 35121 Padova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Sandri
authors.affiliation: Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy; Department of Biology, University of Padova, Via C. Colombo 3, 35121 Padova, Italy. Electronic address: luca.scorrano@unipd.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Scorrano
mesh_terms: D000818:Animals; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010101:Oxygen Consumption; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D045304:Cytochromes c; D020558:GTP Phosphohydrolases; C498809:Opa1 protein, mouse