FIGURE 3.

Oxidative stress and Ca²⁺ signaling. (A) Reactive nitrogen/oxygen species alter the sensitivity of transporters and pumps to Ca²⁺. Cytosolic Ca²⁺ overload is induced by IP3R stimulation, and SERCA/PMCA inhibition. (B) Oxidative stress tolerance is sustained by several Ca²⁺-dependent mechanisms, including PMCA overexpression, activation of anti-apoptotic signaling pathways, and mPTP desensitization. The binding of HK to VDAC contributes to reduced O₂^– leakage by lowering ΔΨm. These mechanisms are used by cancer cells to mediate resistance to ROS-producing anticancer drugs.