Fig. 4.

Hypothetical scheme depicting the regulation of mitochondrial O₂⁻ production and OXPHOS by S-glutathionylation. When H₂O₂ is high and 2GSH/GSSG is low in mitochondria, Odh, Complex I, and ATP synthase are temporarily S-glutathionylated to diminish NADH production and limit electron flow through the respiratory chain. Although this may diminish mitochondrial ATP production S-glutathionylation will limit O₂⁻ and H₂O₂ production by mitochondria. In addition, S-glutathionylation of ATP synthase may also prevent ATP hydrolysis and the pumping of protons back to the intermembrane space. This would effectively maintain a lower membrane potential and limit ROS genesis. Once ROS levels have decreased and the 2GSH/GSSG ratio is restored Grx2 deglutathionylates Complex I and potentially Odh and ATP synthase which restores mitochondrial ATP production.