TRPM8 Regulates Mitochondrial Ca 2+ ‐Dynamics, Temperature and Endoplasmic Reticulum‐Mitochondrial Contact Points in T Cell

ABSTRACT TRPM8 is a cold temperature‐sensitive and non‐selective Ca 2+ ‐channel. Previously we have observed that TRPM8 is endogenously expressed and affects T cell activation process. Now, we report that TRPM8 regulates functions of mitochondria and ER, two important sub‐cellular compartments. Pharmacological modulation of TRPM8 and/or due to TCR‐treatment regulates mitochondrial Ca 2+ , ATP, membrane potential, cardiolipin level and mitochondrial temperature in a context‐dependent manner. In addition, TRPM8 alters the relative temperature of mitochondria and ER, ER‐mitochondrial contact points, mainly at the immunological synapse (IS), and thus TRPM8 has the potential to affect the overall cellular functions. Our data suggests both, i.e., the presence and enrichment of TRPM8 in the IS of T cells. We suggest that TRPM8 is a crucial regulator of Ca 2+ ‐signalling in T cells and significantly contributes to Ca 2+ ‐buffering by modulating cellular and sub‐cellular organelle functions. These findings are useful to understand the functions of T cells in different pathological conditions.