Your browser doesn't support javascript.
loading
Loss of OMA1 delays neurodegeneration by preventing stress-induced OPA1 processing in mitochondria.
Korwitz, Anne; Merkwirth, Carsten; Richter-Dennerlein, Ricarda; Tröder, Simon E; Sprenger, Hans-Georg; Quirós, Pedro M; López-Otín, Carlos; Rugarli, Elena I; Langer, Thomas.
Afiliación
  • Korwitz A; Institute of Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany.
  • Merkwirth C; Institute of Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany.
  • Richter-Dennerlein R; Institute of Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany.
  • Tröder SE; Institute of Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany.
  • Sprenger HG; Institute of Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany.
  • Quirós PM; Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo 33006, Spain.
  • López-Otín C; Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo 33006, Spain.
  • Rugarli EI; Institute of Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany Center for Molecular Medicine, University of Cologne, 50931 Cologne, Germany.
  • Langer T; Institute of Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany Center for Molecular Medicine, University of Cologne, 50931 Cologne, Germany Max Planck Institute for Biology of Aging, 50931 Cologne, Germany
J Cell Biol ; 212(2): 157-66, 2016 Jan 18.
Article en En | MEDLINE | ID: mdl-26783299
Proteolytic cleavage of the dynamin-like guanosine triphosphatase OPA1 in mitochondria is emerging as a central regulatory hub that determines mitochondrial morphology under stress and in disease. Stress-induced OPA1 processing by OMA1 triggersmitochondrial fragmentation, which is associated with mitophagy and apoptosis in vitro. Here, we identify OMA1 as a critical regulator of neuronal survival in vivo and demonstrate that stress-induced OPA1 processing by OMA1 promotes neuronal death and neuroinflammatory responses. Using mice lacking prohibitin membrane scaffolds as a model of neurodegeneration, we demonstrate that additional ablation of Oma1 delays neuronal loss and prolongs lifespan. This is accompanied by the accumulation of fusion-active, long OPA1 forms, which stabilize the mitochondrial genome but do not preserve mitochondrial cristae or respiratory chain supercomplex assembly in prohibitin-depleted neurons. Thus, long OPA1 forms can promote neuronal survival independently of cristae shape, whereas stress-induced OMA1 activation and OPA1 cleavage limit mitochondrial fusion and promote neuronal death.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Mitocondriales / Metaloproteasas / GTP Fosfohidrolasas / Mitocondrias / Degeneración Nerviosa Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Cell Biol Año: 2016 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Mitocondriales / Metaloproteasas / GTP Fosfohidrolasas / Mitocondrias / Degeneración Nerviosa Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Cell Biol Año: 2016 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos