fig1

Figure 1. Short-term response to oxidative stress. The initial response to oxidative stress primarily relies on the activity of antioxidant molecules, which donate electrons to ROS to reduce the oxidative state. To continue functioning as antioxidants, these molecules must be replenished, by receiving electrons from NADPH. ROS, through the oxidation of cysteine residues on the ATM protein, leads to increased ATM activity. In turn, ATM activates the G6PD enzyme, which enhances the production of NADPH from NADP⁺. This process has two immediate consequences: the generation of more NADPH and the redirection of glucose-6-phosphate from oxidative phosphorylation in the mitochondria to the nucleotide synthesis pathway. Consequently, this results in reduced ROS production. Additionally, ROS has a direct impact on mitochondria by oxidizing cysteine residues in complexes I, III, and IV, leading to decreased oxidative phosphorylation. ROS: Reactive oxygen species; NADPH: nicotinamide adenine dinucleotide phosphate; ATM: Ataxia Telangiectasia Mutated; G6PD: glucose-6-phosphate dehydrogenase; NADP⁺: nicotinamide adenine dinucleotide phosphate.