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• W2883403929 endingPage "1150" @default.
• W2883403929 startingPage "1138" @default.
• W2883403929 abstract "To unveil what controls mitochondrial ROS detoxification, the NADPH supply and GSH/GSSG recycling for oxidative stress management were analyzed in cancer and non-cancer mitochondria. Therefore, proteomic and kinetomic analyses were carried out of the mitochondrial (i) NADPH producing and (ii) GSH/GSSG recycling enzymes associated to oxidative stress management. The protein contents of the eight enzymes analyzed were similar or even higher in AS-30D rat hepatoma mitochondria (HepM) than in rat liver (RLM) and rat heart (RHM) mitochondria, suggesting that the NADPH/GSH/ROS pathway was fully functional in cancer mitochondria. The Vmax values of IDH-2 were much greater than those of GDH, TH and ME, suggesting that IDH-2 is the predominant NADPH producer in the three mitochondrial types; in fact, the GDH reverse reaction was favored. The Vmax values of GR and GPx were lower in HepM than in RLM, suggesting that the oxidative stress management is compromised in cancer mitochondria. The Km values of IDH-2, GR and GPx were all similar among the different mitochondrial types. Kinetic modeling revealed that the oxidative stress management was mainly controlled by GR, GPx and IDH. Modeling and experimentation also revealed that, due to their higher IDH-2 activity and lower GPx activity presumably by acetylation, HepM (i) showed higher steady-state NADPH levels; (ii) required greater peroxide concentrations to achieve reliable steady-state fluxes and metabolite concentration; and (iii) endured higher peroxide concentrations without collapsing their GSH/GSSG ratios. Then, to specifically prompt lower GSH/GSSG ratios under oxidative stress thus compromising cancer mitochondria functioning, GPx should be re-activated." @default.
• W2883403929 created "2018-08-03" @default.
• W2883403929 creator A5002401572 @default.
• W2883403929 creator A5013146093 @default.
• W2883403929 creator A5013209374 @default.
• W2883403929 creator A5021751498 @default.
• W2883403929 creator A5039197501 @default.
• W2883403929 creator A5077059969 @default.
• W2883403929 date "2018-10-01" @default.
• W2883403929 modified "2023-10-18" @default.
• W2883403929 title "Control of the NADPH supply and GSH recycling for oxidative stress management in hepatoma and liver mitochondria" @default.
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• W2883403929 doi "https://doi.org/10.1016/j.bbabio.2018.07.008" @default.

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