Мақола

The cristae modulator Optic atrophy 1 requires mitochondrial ATP synthase oligomers to safeguard mitochondrial function

Rubén Quintana–CabreraCIBERFES, Institute of Health Carlos III, Madrid, SpainCharlotte QuirinDepartment of Biology, University of Padua, 35121, Padua, ItalyChristina GlytsouDepartment of Biology, University of Padua, 35121, Padua, ItalyMauro CorradoDepartment of Biology, University of Padua, 35121, Padua, ItalyAndrea UrbaniDepartment of Biomedical Sciences, University of Padua, Padua, 35121, ItalyAnna PellattieroDepartment of Biology, University of Padua, 35121, Padua, ItalyEnrique CalvoCentro Nacional de Investigaciones Cardiovasculares Carlos III, 28029, Madrid, SpainJesús VázquezCentro Nacional de Investigaciones Cardiovasculares Carlos III, 28029, Madrid, SpainJosé Antonio Enrı́quezCIBERFES, Institute of Health Carlos III, Madrid, SpainChristoph GerleCore Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi, JapanMaría Eugenia SorianoInstitute of Neuroscience, Consiglio Nazionale delle Ricerche, Padua, ItalyPaolo BernardiDepartment of Biomedical Sciences, University of Padua, Padua, 35121, ItalyLuca ScorranoDepartment of Biology, University of Padua, 35121, Padua, Italy. [email protected]

2018en

ABI

Аннотация

Abstract It is unclear how the mitochondrial fusion protein Optic atrophy 1 (OPA1), which inhibits cristae remodeling, protects from mitochondrial dysfunction. Here we identify the mitochondrial F 1 F o -ATP synthase as the effector of OPA1 in mitochondrial protection. In OPA1 overexpressing cells, the loss of proton electrochemical gradient caused by respiratory chain complex III inhibition is blunted and this protection is abolished by the ATP synthase inhibitor oligomycin. Mechanistically, OPA1 and ATP synthase can interact, but recombinant OPA1 fails to promote oligomerization of purified ATP synthase reconstituted in liposomes, suggesting that OPA1 favors ATP synthase oligomerization and reversal activity by modulating cristae shape. When ATP synthase oligomers are genetically destabilized by silencing the key dimerization subunit e , OPA1 is no longer able to preserve mitochondrial function and cell viability upon complex III inhibition. Thus, OPA1 protects mitochondria from respiratory chain inhibition by stabilizing cristae shape and favoring ATP synthase oligomerization.

Ҳали таржима қилинмаган

Идентификаторлар

DOI: 10.1038/s41467-018-05655-x

Иқтибослар ва манбалар

2 та иқтибос0 та фойдаланилган манба

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