Details

Autor(en) / Beteiligte

• Lemarie, A
• Huc, L
• Pazarentzos, E
• Mahul-Mellier, A-L
• Grimm, S

Titel

Specific disintegration of complex II succinate:ubiquinone oxidoreductase links pH changes to oxidative stress for apoptosis induction

Ist Teil von

• Cell death and differentiation, 2011-02, Vol.18 (2), p.338-349

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• The formation of reactive oxygen species (ROS) and the change of the intracellular pH (pH i ) are common phenomena during apoptosis. How they are interconnected, however, is poorly understood. Here we show that numerous anticancer drugs and cytokines such as Fas ligand and tumour necrosis factor α provoke intracellular acidification and cause the formation of mitochondrial ROS. In parallel, we found that the succinate:ubiquinone oxidoreductase (SQR) activity of the mitochondrial respiratory complex II is specifically impaired without affecting the second enzymatic activity of this complex as a succinate dehydrogenase (SDH). Only in this configuration is complex II an apoptosis mediator and generates superoxides for cell death. This is achieved by the pH i decline that leads to the specific dissociation of the SDHA/SDHB subunits, which encompass the SDH activity, from the membrane-bound components of complex II that are required for the SQR activity.