Figure 2.

TRPM2 activation by oxidative stress and TRPM2-mediated Ca²⁺ signaling under oxidative stress boosts ROS production in mitochondria. Increased ROS production activates PARP, which produces ADPR, a potent endogenous TRPM2 activator. ADPR activates TRPM2 by binding to the NUDT9-H domain at the C terminus. TRPM2 activation leads to Ca²⁺ influx from the extracellular environment and Ca²⁺ release from lysosomes. TRPM2-mediated Ca²⁺ signaling is critical in regulating a series of cellular functions.