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    Por favor, use este identificador para citar o enlazar este ítem:https://uvadoc.uva.es/handle/10324/66021

    Título
    L‐OPA1 regulates mitoflash biogenesis independently from membrane fusion
    Autor
    Rosselin, Manon
    Santo Domingo Mayoral, JaimeAutoridad UVA Orcid
    Bermont, Flavien
    Giacomello, Marta
    Demaurex, Nicolas
    Año del Documento
    2017
    Editorial
    Embopress
    Descripción
    Producción Científica
    Documento Fuente
    EMBO Reports, March 2017, vol. 18, n. 3, p. 451-463.
    Résumé
    Mitochondrial flashes mediated by optic atrophy 1 (OPA1) fusion protein are bioenergetic responses to stochastic drops in mitochondrial membrane potential (Δψm) whose origin is unclear. Using structurally distinct genetically encoded pH-sensitive probes, we confirm that flashes are matrix alkalinization transients, thereby establishing the pH nature of these events, which we renamed "mitopHlashes". Probes located in cristae or intermembrane space as verified by electron microscopy do not report pH changes during Δψm drops or respiratory chain inhibition. Opa1 ablation does not alter Δψm fluctuations but drastically decreases the efficiency of mitopHlash/Δψm coupling, which is restored by re-expressing fusion-deficient OPA1K301A and preserved in cells lacking the outer-membrane fusion proteins MFN1/2 or the OPA1 proteases OMA1 and YME1L, indicating that mitochondrial membrane fusion and OPA1 proteolytic processing are dispensable. pH/Δψm uncoupling occurs early during staurosporine-induced apoptosis and is mitigated by OPA1 overexpression, suggesting that OPA1 maintains mitopHlash competence during stress conditions. We propose that OPA1 stabilizes respiratory chain supercomplexes in a conformation that enables respiring mitochondria to compensate a drop in Δψm by an explosive matrix pH flash.
    Palabras Clave
    bioenergetics
    membrane fusion
    mitoflash
    OPA1
    ISSN
    1469-221X
    Revisión por pares
    SI
    DOI
    10.15252/embr.201642931
    Patrocinador
    Swiss National Science Fundation (SNSF)
    Ministerio de Ciencia e Innovación
    Version del Editor
    https://www.embopress.org/doi/full/10.15252/embr.201642931
    Propietario de los Derechos
    © 2017 The Authors
    Idioma
    eng
    URI
    https://uvadoc.uva.es/handle/10324/66021
    Tipo de versión
    info:eu-repo/semantics/publishedVersion
    Derechos
    openAccess
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    • DEP06 - Artículos de revista [352]
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