Right Place, Right Function: The Contribution of Subcellular Localization to the Physiological Impact of TRPM2 Channels

The channel TRPM2 forms cation-selective channels and is activated by redox-dynamics, including oxidative stress. Initially described at the plasma membrane, TRPM2 has been found to also localized to intracellular compartments, i.e., nucleus, mitochondria, lysosomes, and the endoplasmic reticulum. Its subcellular distribution appears to influence the Ca2+ signals and signaling pathways associated with each compartment, resulting in distinct cellular outcomes. In cancer, TRPM2 has been implicated in proliferation, survival, autophagy, mitochondrial homeostasis, metabolism, inflammation, and cell death. Notably, TRPM2 can exert opposing effects depending on the cellular context, oxidative state, stimulus, and subcellular localization. These findings suggest that the functional diversity of TRPM2 may arise, at least in part, from its spatial organization within the cell.