Specific disintegration of complex IIsuccinate:ubiquinone oxidoreductase links pHchanges to oxidative stress for apoptosis induction
2011
Lemarie , A(co-premier auteur) (Imperial College London, Hammersmith Campus, London(Royaume Uni). Department of Experimental Medicine and Toxicology) | Huc-Lemarié , Laurence(collaborateur) (INRA , St-Martin-Du-Touch (France). UMR 1331 Toxicologie Alimentaire) | Mahul-Mellier , A-L(collaborateur) (Imperial College London, Hammersmith Campus, London(Royaume Uni). Department of Experimental Medicine and Toxicology) | Grimm , S(auteur de correspondance) (Imperial College London, Hammersmith Campus, London(Royaume Uni). Department of Experimental Medicine and Toxicology)
The formation of reactive oxygen species (ROS) and the change of the intracellular pH (pHi) are common phenomena duringapoptosis. How they are interconnected, however, is poorly understood. Here we show that numerous anticancer drugs andcytokines such as Fas ligand and tumour necrosis factor a provoke intracellular acidification and cause the formation ofmitochondrial ROS. In parallel, we found that the succinate:ubiquinone oxidoreductase (SQR) activity of the mitochondrialrespiratory complex II is specifically impaired without affecting the second enzymatic activity of this complex as a succinatedehydrogenase (SDH). Only in this configuration is complex II an apoptosis mediator and generates superoxides for cell death.This is achieved by the pHi decline that leads to the specific dissociation of the SDHA/SDHB subunits, which encompass the SDHactivity, from the membrane-bound components of complex II that are required for the SQR activity.
اظهر المزيد [+] اقل [-]الكلمات المفتاحية الخاصة بالمكنز الزراعي (أجروفوك)
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