Cell death modulation by transient receptor potential melastatin channels TRPM2 and TRPM7 and their underlying molecular mechanisms

Transient receptor potential melastatin (TRPM) channels are members of the transient receptor potential (TRP) channels, a family of evolutionarily conserved integral membrane proteins. TRPM channels are nonselective cation channels, mediating the influx of various ions including Ca2+, Na+ and Zn2+. The function of TRPM channels is vital for cell proliferation, cell development and cell death. Cell death is a key procedure during embryonic development, organism homeostasis, aging and disease. The category of cell death modalities, beyond the traditionally defined concepts of necrosis, autophagy, and apoptosis, were extended with the discovery of pyroptosis, necroptosis and ferroptosis. As upstream signaling regulators of cell death, TRPM channels have been involved inrelevant pathologies. In this review, we introduced several cell death modalities, then summarized the contribution of TRPM channels (especially TRPM2 and TRPM7) to different cell death modalities and discussed the underlying regulatory mechanisms. Our work highlighted the possibility of TRPM channels as potential therapeutic targets in cell death-related diseases.