{"id":20885,"date":"2026-03-31T15:46:58","date_gmt":"2026-03-31T15:46:58","guid":{"rendered":"https:\/\/drpascalmensah.com\/quand-les-microglies-ne-peuvent-plus-nettoyer-leurs-mitochondries\/"},"modified":"2026-04-17T09:22:39","modified_gmt":"2026-04-17T09:22:39","slug":"microglie-mitochondries-clairance","status":"publish","type":"post","link":"https:\/\/drpascalmensah.com\/fr\/microglie-mitochondries-clairance\/","title":{"rendered":"Quand les microglies ne peuvent plus nettoyer leurs mitochondries"},"content":{"rendered":"\t\t
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La cha\u00eene m\u00e9canistique<\/h3>\t\t\t\t<\/div>\n\t\t\t\t
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De la d\u00e9gradation mitochondriale \u00e0 une neuroinflammation verrouill\u00e9e \u2014 \u00e9tape par \u00e9tape<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t

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1<\/h3>\t\t\t\t<\/div>\n\t\t\t\t
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\n\t\t\t\t\n\t\t\t\t<\/i>\t\t\t\t<\/span>\n\t\t\t<\/div>\n\t\t\t\n\t\t\t\t\t\t
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\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMitochondries endommag\u00e9es\t\t\t\t\t\t<\/span>\n\t\t\t\t\t<\/h3>\n\t\t\t\t\n\t\t\t\t\t\t\t\t\t

\n\t\t\t\t\t\tATP \u2193 ROS \u2191 effondrement du \u0394\u03a8m\t\t\t\t\t<\/p>\n\t\t\t\t\n\t\t\t<\/div>\n\t\t\t\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t

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2<\/h3>\t\t\t\t<\/div>\n\t\t\t\t
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\n\t\t\t\t\n\t\t\t\t<\/path><\/svg>\t\t\t\t<\/span>\n\t\t\t<\/div>\n\t\t\t\n\t\t\t\t\t\t
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\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tD\u00e9faillance des lysosomes\t\t\t\t\t\t<\/span>\n\t\t\t\t\t<\/h3>\n\t\t\t\t\n\t\t\t\t\t\t\t\t\t

\n\t\t\t\t\t\tMitophagie bloqu\u00e9e \u2192 accumulation d\u2019organites endommag\u00e9s\t\t\t\t\t<\/p>\n\t\t\t\t\n\t\t\t<\/div>\n\t\t\t\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t

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3<\/h3>\t\t\t\t<\/div>\n\t\t\t\t
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\n\t\t\t\t\n\t\t\t\t<\/path><\/svg>\t\t\t\t<\/span>\n\t\t\t<\/div>\n\t\t\t\n\t\t\t\t\t\t
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\n\t\t\t\t\t\t\n\t\t\t\t\t\t\t\u00c9chappement de l\u2019ADN mitochondrial (mtDNA)\t\t\t\t\t\t<\/span>\n\t\t\t\t\t<\/h3>\n\t\t\t\t\n\t\t\t\t\t\t\t\t\t

\n\t\t\t\t\t\tLib\u00e9ration dans le cytosol \u2192 activation de cGAS-STING et TLR9\t\t\t\t\t<\/p>\n\t\t\t\t\n\t\t\t<\/div>\n\t\t\t\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t

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4<\/h3>\t\t\t\t<\/div>\n\t\t\t\t
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\n\t\t\t\t\n\t\t\t\t<\/path><\/svg>\t\t\t\t<\/span>\n\t\t\t<\/div>\n\t\t\t\n\t\t\t\t\t\t
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\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInflammation verrouill\u00e9e\t\t\t\t\t\t<\/span>\n\t\t\t\t\t<\/h3>\n\t\t\t\t\n\t\t\t\t\t\t\t\t\t

\n\t\t\t\t\t\tMicroglie \u2192 ph\u00e9notype de type M1 (IL-1\u03b2, TNF-\u03b1, IFN-I)\t\t\t\t\t<\/p>\n\t\t\t\t\n\t\t\t<\/div>\n\t\t\t\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t

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5<\/h3>\t\t\t\t<\/div>\n\t\t\t\t
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\n\t\t\t\t\n\t\t\t\t<\/path><\/svg>\t\t\t\t<\/span>\n\t\t\t<\/div>\n\t\t\t\n\t\t\t\t\t\t
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\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLa boucle se referme\t\t\t\t\t\t<\/span>\n\t\t\t\t\t<\/h3>\n\t\t\t\t\n\t\t\t\t\t\t\t\t\t

\n\t\t\t\t\t\tLes cytokines aggravent encore la dysfonction mitochondriale\t\t\t\t\t<\/p>\n\t\t\t\t\n\t\t\t<\/div>\n\t\t\t\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

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Point cl\u00e9 : il s\u2019agit d\u2019une boucle de r\u00e9troaction positive \u2014 et non d\u2019une cascade lin\u00e9aire<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t

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\u00c9TAPES 1\u20132<\/h2>\t\t\t\t<\/div>\n\t\t\t\t
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Les mitochondries \u00e9chouent. Les lysosomes ne suivent plus. \n<\/h3>\t\t\t\t<\/div>\n\t\t\t\t
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\n\t\t\t\t\n\t\t\t\t<\/path><\/svg>\t\t\t\t<\/span>\n\t\t\t<\/div>\n\t\t\t\n\t\t\t\t\t\t
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\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLa d\u00e9faillance du flux de mitophagie est le goulot d\u2019\u00e9tranglement central\t\t\t\t\t\t<\/span>\n\t\t\t\t\t<\/h3>\n\t\t\t\t\n\t\t\t\t\n\t\t\t<\/div>\n\t\t\t\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t
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Dysfonction de la cha\u00eene respiratoire (ETC)<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
\n\t\t\t\t\t\t\t\t\tLes complexes I et III fuient des \u00e9lectrons \u2192 production de superoxyde \u2192 d\u00e9polarisation membranaire (\u0394\u03a8m \u2193)\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t
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Hyperfission via DRP1<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
\n\t\t\t\t\t\t\t\t\tLes organites endommag\u00e9s se fragmentent plus vite qu\u2019ils ne sont \u00e9limin\u00e9s \u2192 accumulation nette\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t
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D\u00e9faillance de l\u2019acidification lysosomale<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
\n\t\t\t\t\t\t\t\t\tLes cytokines inflammatoires alt\u00e8rent la V-ATPase \u2192 augmentation du pH lysosomal \u2192 le cargo LC3-II n\u2019est pas d\u00e9grad\u00e9\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t
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Boucle de d\u00e9pl\u00e9tion en NAD+<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
\n\t\t\t\t\t\t\t\t\tLes ROS activent PARP1 \u2192 consommation de NAD+ \u2192 baisse de SIRT1\/3 \u2192 diminution de PGC-1\u03b1 \u2192 moins de biogen\u00e8se mitochondriale\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t
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\u00c9TAPES 3\u20134 \u00b7 \u00c9chappement du mtDNA \u2192 verrouillage de l\u2019inflammation<\/h3>\t\t\t\t<\/div>\n\t\t
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Mitophagie
bloqu\u00e9e<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
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  • \n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t<\/path><\/svg>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\tLes mitochondries endommag\u00e9es persistent<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t\t\t
  • \n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t<\/path><\/svg>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\tFer labile + cardiolipine expos\u00e9s<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t\t\t
  • \n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t<\/path><\/svg>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\tLe mtDNA fuit dans le cytosol<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t\t\t
  • \n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t<\/path><\/svg>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\tImpossible \u00e0 d\u00e9grader \u00e0 cause des lysosomes d\u00e9faillants<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t<\/ul>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t
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    Activation des
    capteurs inn\u00e9s<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
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    • \n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t<\/path><\/svg>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\tcGAS d\u00e9tecte l\u2019ADN double brin cytosolique<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t\t\t
    • \n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t<\/path><\/svg>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\tSTING \u2192 IRF3 \u2192 cascade IFN-I<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t\t\t
    • \n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t<\/path><\/svg>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\tTLR9 d\u00e9tecte le mtDNA oxyd\u00e9<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t\t\t
    • \n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t<\/path><\/svg>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\tNLRP3 activ\u00e9 par les mtROS et la cardiolipine<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t<\/ul>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t
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      Inflammation
      verrouill\u00e9e<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
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      • \n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t<\/path><\/svg>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\tProduction soutenue de IFN-I, IL-1\u03b2, TNF-\u03b1<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t\t\t
      • \n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t<\/path><\/svg>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\tPh\u00e9notype microglial de type M1 fix\u00e9<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t\t\t
      • \n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t<\/path><\/svg>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\tPerte de la capacit\u00e9 phagocytaire (M2)<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t\t\t
      • \n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t<\/path><\/svg>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\tLes cytokines aggravent encore la cha\u00eene respiratoire \u2192 boucle<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t<\/ul>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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        \n\t\t\t\t\n\t\t\t\t<\/path><\/svg>\t\t\t\t<\/span>\n\t\t\t<\/div>\n\t\t\t\n\t\t\t\t\t\t
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        \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t Aper\u00e7u thermodynamique : le mtDNA oxyd\u00e9 (ROS d\u00e9pendants du fer) est un agoniste bien plus puissant de TLR9 que le mtDNA natif \u2014 un amplificateur reliant le stress redox \u00e0 l\u2019inflammation chronique.\t\t\t\t\t\t<\/span>\n\t\t\t\t\t<\/h3>\n\t\t\t\t\n\t\t\t\t\n\t\t\t<\/div>\n\t\t\t\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t
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        Connexion #1 \u2014 Mitochondries & lysosomes dans l\u2019immunom\u00e9tabolisme des lymphocytes T<\/h3>\t\t\t\t<\/div>\n\t\t\t\t
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        M\u00eame principe de communication entre organites \u2014 cellule diff\u00e9rente, m\u00eame mode d\u2019\u00e9chec<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t

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        m\u00eame \u00e9chec<\/h4>\t\t\t\t<\/div>\n\t\t
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        Microglies (SNC)<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
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        • \n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t<\/path><\/svg>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\tCellules immunitaires inn\u00e9es du cerveau<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t\t\t
        • \n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t<\/path><\/svg>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\tN\u00e9cessitent l\u2019ATP issu de l\u2019OXPHOS pour la phagocytose<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t\t\t
        • \n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t<\/path><\/svg>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\tD\u00e9faillance mito-lysosomale \u2192 lib\u00e9ration de mtDNA \u2192 cGAS-STING<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t\t\t
        • \n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t<\/path><\/svg>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\tVerrouillage en ph\u00e9notype pro-inflammatoire M1<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t\t\t
        • \n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t<\/path><\/svg>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\tR\u00e9sultat : neuroinflammation, comportements d\u00e9pressifs<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t<\/ul>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t
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          Lymphocytes T (p\u00e9riph\u00e9rie)<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
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            \n\t\t\t\t\t\t\t
          • \n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t<\/path><\/svg>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\tCellules immunitaires adaptatives<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t\t\t
          • \n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t<\/path><\/svg>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\tLes lysosomes sont essentiels au recyclage du TCR et \u00e0 la m\u00e9moire<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t\t\t
          • \n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t<\/path><\/svg>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\tD\u00e9faillance mito-lysosomale \u2192 autophagie alt\u00e9r\u00e9e \u2192 \u00e9puisement des cellules T<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t\t\t
          • \n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t<\/path><\/svg>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\tPh\u00e9notype dysfonctionnel (PD-1+, TIM-3+)<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t\t\t
          • \n\t\t\t\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t<\/path><\/svg>\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t\tR\u00e9sultat : immunosuppression, perte d\u2019immunit\u00e9 anti-tumorale et antivirale<\/span>\n\t\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t\t\t<\/ul>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t\t\t\t\t

            Principe unificateur : l\u2019\u00e9chec du contr\u00f4le qualit\u00e9 des organites d\u00e9termine le destin inflammatoire \u2014 ind\u00e9pendamment du type cellulaire<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t

            \n\t\t\t\t\t
            \n\t\t\t\t
            \n\t\t\t\t\t

            Connexion #2 \u2014 Dysfonction mitochondriale et polarisation des macrophages dans la septic\u00e9mie<\/h3>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t\t\t\t\t

            Ji, Zhang et al. \u2014 Fronti\u00e8res en immunologie | L’analogue p\u00e9riph\u00e9rique des macrophages de l’\u00e9chec de la mitophagie microgliale <\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t

            \n\t\t\t\t
            \n\t\t\t\t\t

            <\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t

            Microglie \u2014 D\u00e9pression<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t

            Macrophage \u2014 Sepsis<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t

            Type cellulaire<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t

            Microglies (SNC)<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t

            Macrophages (p\u00e9riph\u00e9riques \/ h\u00e9patiques \/ pulmonaires)<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t

            D\u00e9clencheur<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t

            Stress chronique, accumulation de ROS<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t

            Infection, endotoxine (LPS)<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t

            Mode de d\u00e9faillance mitochondriale<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t

            Acidification lysosomale alt\u00e9r\u00e9e \u2192 blocage de la mitophagie<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t

            D\u00e9couplage de la cha\u00eene respiratoire, perte de \u0394\u03a8m, explosion de ROS<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t

            Signalisation DAMP<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t

            mtDNA via cGAS-STING \/ TLR9<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t

            mtROS et mtDNA via NLRP3, TLR9<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t

            R\u00e9ponse inflammatoire<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t

            IFN-I, IL-1\u03b2 \u2192 neuroinflammation<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t

            IL-6, TNF-\u03b1 \u2192 temp\u00eate cytokinique \u2192 paralysie immunitaire<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t

            D\u00e9faut de r\u00e9solution<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t

            Phagocytose d\u00e9fectueuse<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t

            Polarisation M2 alt\u00e9r\u00e9e \u2192 immunosuppression prolong\u00e9e<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t

            Th\u00e9rapies communes<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t

            Pr\u00e9curseurs NAD+, inducteurs de mitophagie<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t

            Antioxydants mitochondriaux, restauration m\u00e9tabolique<\/h4>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t
            \n\t\t\t\t\t
            \n\t\t\t\t
            \n\t\t\t\t\t

            Connexion n\u00b0 3 \u2014 Axe IRG1-itaconate dans l'immunom\u00e9tabolisme<\/h3>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t\t\t\t\t

            Un m\u00e9tabolite anti-inflammatoire produit par les macrophages<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t

            \n\t\t
            \n\t\t
            \n\t\t\t\t
            \n\t\t\t\t\t

            Stimulus inflammatoire<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t\t\t\t\tLPS \/ cytokines \/ ROS\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t\t\t
            \n\t\t\t
            \n\t\t\t<\/i>\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t
            \n\t\t\t\t
            \n\t\t\t\t\t

            IRG1 \u2192 production d\u2019itaconate<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t\t\t\t\tAconitate d\u00e9carboxylase dans le cycle de Krebs : aconitate \u2192 itaconate ; bloque \u00e9galement la succinate d\u00e9shydrog\u00e9nase (complexe II).\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t\t\t
            \n\t\t\t
            \n\t\t\t<\/i>\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t
            \n\t\t\t\t
            \n\t\t\t\t\t

            Alkylates d'itaconate KEAP1<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t\t\t\t\tL’itaconate \u00e9lectrophile modifie les cyst\u00e9ines de KEAP1 \u2192 Nrf2 est lib\u00e9r\u00e9 et transloqu\u00e9 vers le noyau\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t\t\t
            \n\t\t\t
            \n\t\t\t<\/i>\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t
            \n\t\t\t\t
            \n\t\t\t\t\t

            Effets en aval du NRF2<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t\t\t\t\t

            \u2191 biogen\u00e8se lysosomale (TFEB, V-ATPase)
            \u2191 capacit\u00e9 de mitophagie
            \u2191 g\u00e8nes antioxydants (NQO1, HO-1, SOD)
            \u2193 activation de l\u2019inflammasome NLRP3<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t

            \n\t\t
            \n\t\t\t\t
            \n\t\t\t\t\t

            Inhibition de SDH \u2192 moins de mtROS<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t\t\t\t\tL’itaconate inhibe de mani\u00e8re comp\u00e9titive le complexe II \u2192 r\u00e9duit le transport inverse d’\u00e9lectrons \u2192 la production de ROS mitochondriales diminue \u2192 \u0394\u03a8m est prot\u00e9g\u00e9\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t
            \n\t\t\t\t
            \n\t\t\t\t\t

            Nrf2 \u2192 restauration lysosomale<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t\t\t\t\tLa co-activation de TFEB restaure l’acidification lysosomale (sous-unit\u00e9s de la V-ATPase) et la biogen\u00e8se \u2192 d\u00e9bloque la fusion mitophagosome-lysosome \u2192 r\u00e9tablit la communication entre les organites\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t
            \n\t\t\t\t
            \n\t\t\t\t\t

            L'hypoth\u00e8se en amont<\/h4>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t\t\t\t\t

            Si l’itaconate endog\u00e8ne (ou ses d\u00e9riv\u00e9s exog\u00e8nes : 4-OI, DIMCI) restaure le dialogue mitochondries-lysosomes dans la microglie, la reprogrammation m\u00e9tabolique \u00e0 elle seule pourrait rompre le cycle de neuroinflammation, sans bloquer les cytokines en aval.<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t

            \n\t\t\t\t\t
            \n\t\t\t\t
            \n\t\t\t\t\t

            Restauration d'une faible entropie<\/h3>\t\t\t\t<\/div>\n\t\t\t\t
            \n\t\t\t\t\t\t\t\t\t

            Strat\u00e9gies th\u00e9rapeutiques ciblant l’axe d\u00e9faillance du contr\u00f4le qualit\u00e9 des organites \u2192 inflammation<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t

            \n\t\t\t\t
            \n\t\t\t\t\t\t\t
            \n\n\t\t\t\t\t\t
            \n\t\t\t\t\n\t\t\t\t<\/i>\t\t\t\t<\/span>\n\t\t\t<\/div>\n\t\t\t\n\t\t\t\t\t\t
            \n\n\t\t\t\t\t\t\t\t\t

            \n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPr\u00e9curseurs de NAD+\t\t\t\t\t\t<\/span>\n\t\t\t\t\t<\/h3>\n\t\t\t\t\n\t\t\t\t\t\t\t\t\t

            \n\t\t\t\t\t\tNR \/ NMN \u2192 r\u00e9activation SIRT1\/3, PGC-1\u03b1 \u2192 am\u00e9lioration OXPHOS et mitophagie\t\t\t\t\t<\/p>\n\t\t\t\t\n\t\t\t<\/div>\n\t\t\t\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t

            \n\t\t\t\t\t\t\t
            \n\n\t\t\t\t\t\t
            \n\t\t\t\t\n\t\t\t\t<\/path><\/svg>\t\t\t\t<\/span>\n\t\t\t<\/div>\n\t\t\t\n\t\t\t\t\t\t
            \n\n\t\t\t\t\t\t\t\t\t

            \n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInducteurs de mitophagie\t\t\t\t\t\t<\/span>\n\t\t\t\t\t<\/h3>\n\t\t\t\t\n\t\t\t\t\t\t\t\t\t

            \n\t\t\t\t\t\tUrolithine A, rapamycine \u2192 activation PINK1\/Parkin\t\t\t\t\t<\/p>\n\t\t\t\t\n\t\t\t<\/div>\n\t\t\t\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t

            \n\t\t\t\t\t\t\t
            \n\n\t\t\t\t\t\t
            \n\t\t\t\t\n\t\t\t\t<\/i>\t\t\t\t<\/span>\n\t\t\t<\/div>\n\t\t\t\n\t\t\t\t\t\t
            \n\n\t\t\t\t\t\t\t\t\t

            \n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAcidifiants lysosomaux\t\t\t\t\t\t<\/span>\n\t\t\t\t\t<\/h3>\n\t\t\t\t\n\t\t\t\t\t\t\t\t\t

            \n\t\t\t\t\t\tActivation V-ATPase, TFEB \u2192 restauration du pH lysosomal\t\t\t\t\t<\/p>\n\t\t\t\t\n\t\t\t<\/div>\n\t\t\t\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t

            \n\t\t\t\t\t\t\t
            \n\n\t\t\t\t\t\t
            \n\t\t\t\t\n\t\t\t\t<\/path><\/svg>\t\t\t\t<\/span>\n\t\t\t<\/div>\n\t\t\t\n\t\t\t\t\t\t
            \n\n\t\t\t\t\t\t\t\t\t

            \n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBlocage cGAS-STING \/ TLR9\t\t\t\t\t\t<\/span>\n\t\t\t\t\t<\/h3>\n\t\t\t\t\n\t\t\t\t\t\t\t\t\t

            \n\t\t\t\t\t\tH-151, C176 \u2192 r\u00e9duction de l\u2019inflammation\t\t\t\t\t<\/p>\n\t\t\t\t\n\t\t\t<\/div>\n\t\t\t\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

            \n\t\t\t\t\t\t\t\t\t

            Principe fondamental : le chemin vers une faible entropie passe par les organites \u2014 et non en les contournant.<\/p><\/div><\/div><\/div><\/div>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"

            Des mitochondries endommag\u00e9es peuvent-elles pi\u00e9ger le cerveau dans une inflammation chronique et conduire \u00e0 la d\u00e9pression ?
            \nCet article explore comment la d\u00e9faillance du dialogue mitochondrie\u2013lysosome enferme les microglies dans une boucle inflammatoire auto-entretenue, et comment ce m\u00e9canisme est li\u00e9 \u00e0 la septic\u00e9mie, au dysfonctionnement des lymphocytes T et \u00e0 l\u2019axe IRG1\u2013itaconate.<\/p>\n","protected":false},"author":1,"featured_media":20884,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"set","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[166],"tags":[210,216],"class_list":["post-20885","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-mitochondrie","tag-mitochondries","tag-neurosciences"],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/drpascalmensah.com\/fr\/wp-json\/wp\/v2\/posts\/20885","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/drpascalmensah.com\/fr\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/drpascalmensah.com\/fr\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/drpascalmensah.com\/fr\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/drpascalmensah.com\/fr\/wp-json\/wp\/v2\/comments?post=20885"}],"version-history":[{"count":6,"href":"https:\/\/drpascalmensah.com\/fr\/wp-json\/wp\/v2\/posts\/20885\/revisions"}],"predecessor-version":[{"id":21439,"href":"https:\/\/drpascalmensah.com\/fr\/wp-json\/wp\/v2\/posts\/20885\/revisions\/21439"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/drpascalmensah.com\/fr\/wp-json\/wp\/v2\/media\/20884"}],"wp:attachment":[{"href":"https:\/\/drpascalmensah.com\/fr\/wp-json\/wp\/v2\/media?parent=20885"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/drpascalmensah.com\/fr\/wp-json\/wp\/v2\/categories?post=20885"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/drpascalmensah.com\/fr\/wp-json\/wp\/v2\/tags?post=20885"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}