2026-06-14T05:05:03Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/65372024-10-31T11:40:12Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607

00925njm 22002777a 4500 dc Quintana-Cabrera, Ruben author Quirin, Charlotte author Glytsou, Christina author Corrado, Mauro author Urbani, Andrea author Pellattiero, Anna author Calvo, Enrique author Vazquez, Jesus author Enriquez, Jose Antonio author Gerle, Christoph author Soriano, Maria Eugenia author Bernardi, Paolo author Scorrano, Luca author 2018 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 F1Fo-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. Nat Commun. 2018; 9(1):3399 10.1038/s41467-018-05655-x 2041-1723 Nature Communications 30143614 http://hdl.handle.net/20.500.12105/6537 PERMEABILITY TRANSITION PORE COMPLEX III DEFICIENCY CYTOCHROME-C RELEASE OXIDATIVE-PHOSPHORYLATION F1F0-ATP SYNTHASE SUPRAMOLECULAR ORGANIZATION LIVER-MITOCHONDRIA INHIBITOR PROTEIN INNER MEMBRANE SUBUNIT-G The cristae modulator Optic atrophy 1 requires mitochondrial ATP synthase oligomers to safeguard mitochondrial function