# TRPM8 Regulates Mitochondrial Ca2+‐Dynamics, Temperature and Endoplasmic Reticulum‐Mitochondrial Contact Points in T Cell

## TL;DR

TRPM8, a cold-sensitive calcium channel, influences mitochondrial and ER functions in T cells, affecting calcium signaling and cell activity.

## Contribution

TRPM8's role in regulating mitochondrial calcium dynamics and ER-mitochondrial contacts in T cells is newly identified.

## Key findings

- TRPM8 modulates mitochondrial calcium, ATP, and membrane potential in T cells.
- TRPM8 affects ER-mitochondrial contact points and temperature at the immunological synapse.
- TRPM8 contributes to calcium buffering and sub-cellular organelle functions in T cells.

## Abstract

TRPM8 is a cold temperature‐sensitive and non‐selective Ca2+‐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 Ca2+, 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 Ca2+‐signalling in T cells and significantly contributes to Ca2+‐buffering by modulating cellular and sub‐cellular organelle functions. These findings are useful to understand the functions of T cells in different pathological conditions.