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A mitochondrial membrane-bridging machinery mediates signal transduction of intramitochondrial oxidation.
Li, Li; Conradson, Devon M; Bharat, Vinita; Kim, Min Joo; Hsieh, Chung-Han; Minhas, Paras S; Papakyrikos, Amanda M; Durairaj, Aarooran Sivakumaran; Ludlam, Anthony; Andreasson, Katrin I; Partridge, Linda; Cianfrocco, Michael A; Wang, Xinnan.
Afiliación
  • Li L; Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Conradson DM; Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Bharat V; Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Kim MJ; Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Hsieh CH; Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Minhas PS; Department of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
  • Papakyrikos AM; Neurosciences Intradepartmental Graduate Program, Stanford University School of Medicine, Stanford, CA, USA.
  • Durairaj AS; Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Ludlam A; Graduate Program in Developmental Biology, Stanford University School of Medicine, Stanford, CA, USA.
  • Andreasson KI; Department of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
  • Partridge L; Life Sciences Institute & Department of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA.
  • Cianfrocco MA; Department of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
  • Wang X; Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA, USA.
Nat Metab ; 3(9): 1242-1258, 2021 09.
Article en En | MEDLINE | ID: mdl-34504353
Mitochondria are the main site for generating reactive oxygen species, which are key players in diverse biological processes. However, the molecular pathways of redox signal transduction from the matrix to the cytosol are poorly defined. Here we report an inside-out redox signal of mitochondria. Cysteine oxidation of MIC60, an inner mitochondrial membrane protein, triggers the formation of disulfide bonds and the physical association of MIC60 with Miro, an outer mitochondrial membrane protein. The oxidative structural change of this membrane-crossing complex ultimately elicits cellular responses that delay mitophagy, impair cellular respiration and cause oxidative stress. Blocking the MIC60-Miro interaction or reducing either protein, genetically or pharmacologically, extends lifespan and health-span of healthy fruit flies, and benefits multiple models of Parkinson's disease and Friedreich's ataxia. Our discovery provides a molecular basis for common treatment strategies against oxidative stress.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Membranas Mitocondriales / Mitocondrias Límite: Animals / Humans Idioma: En Revista: Nat Metab Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Membranas Mitocondriales / Mitocondrias Límite: Animals / Humans Idioma: En Revista: Nat Metab Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania