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

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 p...

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Detalles Bibliográficos
Autores: Quintana-Cabrera, Ruben, Quirin, Charlotte, Glytsou, Christina, Corrado, Mauro, Urbani, Andrea, Pellattiero, Anna, Calvo, Enrique, Vazquez, Jesus, Enriquez, Jose Antonio, Gerle, Christoph, Soriano, Maria Eugenia, Bernardi, Paolo, Scorrano, Luca
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/6537
Acceso en línea:http://hdl.handle.net/20.500.12105/6537
Access Level:acceso abierto
Palabra clave:PERMEABILITY TRANSITION PORE
COMPLEX III DEFICIENCY
CYTOCHROME-C RELEASE
OXIDATIVE-PHOSPHORYLATION
F1F0-ATP SYNTHASE
SUPRAMOLECULAR ORGANIZATION
LIVER-MITOCHONDRIA
INHIBITOR PROTEIN
INNER MEMBRANE
SUBUNIT-G
Descripción
Sumario: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.

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