TRPV1 Channels Are New Players in the Reticulum–Mitochondria Ca2+ Coupling in a Rat Cardiomyoblast Cell Line

Abstract

The Ca2+ release in microdomains formed by intercompartmental contacts, such as mitochondria-associated endoplasmic reticulum membranes (MAMs), encodes a signal that contributes to Ca2+ homeostasis and cell fate control. However, the composition and function of MAMs remain to be fully defined. Here, we focused on the transient receptor potential vanilloid 1 (TRPV1), a Ca2+-permeable ion channel and a polymodal nociceptor. We found TRPV1 channels in the reticular membrane, including some at MAMs, in a rat cardiomyoblast cell line (SV40-transformed H9c2) by Western blotting, immunostaining, cell fractionation, and proximity ligation assay. We used chemical and genetic probes to perform Ca2+ imaging in four cellular compartments: the endoplasmic reticulum (ER), cytoplasm, mitochondrial matrix, and mitochondrial surface. Our results showed that the ER Ca2+ released through TRPV1 channels is detected at the mitochondrial outer membrane and transferred to the mitochondria. Finally, we observed that prolonged TRPV1 modulation for 30 min alters the intracellular Ca2+ equilibrium and influences the MAM structure or the hypoxia/reoxygenation-induced cell death. Thus, our study provides the first evidence that TRPV1 channels contribute to MAM Ca2+ exchanges.

10th European Calcium Society symposium: The Ca2+-signaling toolkit in cell function, health and disease

“…Moreover, prolonged/sustained TRPV1 activation decreases MAM interactions, thereby reducing mitochondrial Ca 2+ accumulation. Furthermore, pharmacological activation of TRPV1 during the pre-conditioning phase of hypoxia/reoxygenation counteracted the associated cell death ( Tessier et al, 2023 ).…”

So close, yet so far away: the relationship between MAM and cardiac disease

“…Nolwenn Tessier et al demonstrated for the first time that transient receptor potential vanilloid type 1 (TRPV1) is involved in regulating MAM-mediated Ca 2+ exchange ( 60 ). RTX, a TPRV1 agonist, slowly increased the mitochondrial Ca 2+ content, whereas iRTX had the opposite effect.…”

“…Activation of TRPV1 by RTX resulted in an elevation of Ca 2+ concentration in specific areas on the mitochondrial surface (Ca 2+ hot spots), which could directly mobilize Ca 2+ from the ER to mitochondria and trigger the remodeling of MAM. Apart from Ca 2+ transfer, sustained activation of TRPV1 also reduced the contacts between the ER and mitochondria, which might mutually decrease the Ca 2+ content within mitochondria ( 60 ). Sun et al demonstrated that TRPV1 activation at the beginning of H/R is harmful to cell survival, and inhibiting it protects cells from death ( 61 ).…”

“…Sun et al demonstrated that TRPV1 activation at the beginning of H/R is harmful to cell survival, and inhibiting it protects cells from death ( 61 ). In H/R conditions, the results showed a protective effect of RTX by reducing cell mortality by ∼18% compared to control H/R only when RTX was applied before hypoxia ( 60 ). The controversial effects of the pharmacological activation of TRPV1 may be related to the treatment window, which should be finely tuned with respect to ischemia ( Figure 2 ).…”