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Cell Metab. 2015 Jun 2;21(6):834-44. doi: 10.1016/j.cmet.2015.05.007.

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

Author information

1
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.
2
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.
3
Department of Biomedical Sciences, University of Padova, Via C. Colombo 3, 35121 Padova, Italy.
4
Institute of Neuroscience, National Research Council of Italy (CNR), Via C. Colombo 3, 35121 Padova, Italy.
5
Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy.
6
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.
7
Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy.
8
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.

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.

PMID:
26039448
PMCID:
PMC4457892
DOI:
10.1016/j.cmet.2015.05.007
[Indexed for MEDLINE]
Free PMC Article

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