Identification of a human mitochondrial isoform of TRPV1: a thermostat regulating mitochondrial maximal temperature?
Abstract
Mitochondria are well known to produce ATP for cell energy requirements and thermogenesis simultaneously by the respiratory chain, with a potential optimum temperature of 50 °C, while deleterious overheating should be prevented by a yet unknown system. Here, we report the identification of a human Transient Receptor Potential Vanilloid 1 (mitoTRPV1) alternative isoform located in the mitochondrial inner membrane, which acts as a thermostat regulating mitochondrial maximal temperature. The ubiquitously expressed mitoTRPV1 open reading frame overlaps TRPV1 exons 1 and 2 and intron 2 in a + 1 frame, encoding for an effective 150 amino-acid N-terminal mitochondrial targeting sequence (MTS) conserved amongst mammalian species, followed by the 687 amino acids of the TRPV1 C-terminal sequence. Pharmacological activation of mitoTRPV1 induces a low cytoplasmic Ca 2+ increase and mitochondrial cooling without modification of mitochondrial respiration and ATP production. We conclude that, in our experimental conditions, mitoTRPV1 acts as a thermostat to promote mitochondrial thermolysis without impairing respiration and ATP production. They point to the potential implication of mitoTRPV1 in human diseases related to temperature dysregulation, and should be further studied in physiological conditions in cellular and animal models expressing mitoTRPV1 endogenously.
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BibTeX
@article{beignon2026identification,
title = {{Identification of a human mitochondrial isoform of TRPV1: a thermostat regulating mitochondrial maximal temperature?}},
author = {Florian Beignon and Sylvie Ducreux and Artur Wardaszka and Joanna Bujak and Léa Tuifua and Camille Blaecke and Caroline Bosson and Lucie Maujean and Florentin Moulin and Yannick Le Dantec and Morgane Lemao and Adélie Mellinger and Méline Wery and David Goudenège and Arnaud Chevrollier and Salim Khiati and Hélène Tricoire-Leignel and Naig Gueguen and Nathalie Roux-Buisson and Julien Fauré and Piotr Bednarczyk and Guy Lenaers and César Mattei},
journal = {Cellular and Molecular Life Sciences},
year = {2026},
month = jul,
doi = {10.1007/s00018-026-06360-5},
url = {https://hal.science/hal-05766683v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Identification of a human mitochondrial isoform of TRPV1: a thermostat regulating mitochondrial maximal temperature?
AU - Florian Beignon
AU - Sylvie Ducreux
AU - Artur Wardaszka
AU - Joanna Bujak
AU - Léa Tuifua
AU - Camille Blaecke
AU - Caroline Bosson
AU - Lucie Maujean
AU - Florentin Moulin
AU - Yannick Le Dantec
AU - Morgane Lemao
AU - Adélie Mellinger
AU - Méline Wery
AU - David Goudenège
AU - Arnaud Chevrollier
AU - Salim Khiati
AU - Hélène Tricoire-Leignel
AU - Naig Gueguen
AU - Nathalie Roux-Buisson
AU - Julien Fauré
AU - Piotr Bednarczyk
AU - Guy Lenaers
AU - César Mattei
PY - 2026
DA - 2026/07/23
JO - Cellular and Molecular Life Sciences
DO - 10.1007/s00018-026-06360-5
UR - https://hal.science/hal-05766683v1
AB - Mitochondria are well known to produce ATP for cell energy requirements and thermogenesis simultaneously by the respiratory chain, with a potential optimum temperature of 50 °C, while deleterious overheating should be prevented by a yet unknown system. Here, we report the identification of a human Transient Receptor Potential Vanilloid 1 (mitoTRPV1) alternative isoform located in the mitochondrial inner membrane, which acts as a thermostat regulating mitochondrial maximal temperature. The ubiquitously expressed mitoTRPV1 open reading frame overlaps TRPV1 exons 1 and 2 and intron 2 in a + 1 frame, encoding for an effective 150 amino-acid N-terminal mitochondrial targeting sequence (MTS) conserved amongst mammalian species, followed by the 687 amino acids of the TRPV1 C-terminal sequence. Pharmacological activation of mitoTRPV1 induces a low cytoplasmic Ca 2+ increase and mitochondrial cooling without modification of mitochondrial respiration and ATP production. We conclude that, in our experimental conditions, mitoTRPV1 acts as a thermostat to promote mitochondrial thermolysis without impairing respiration and ATP production. They point to the potential implication of mitoTRPV1 in human diseases related to temperature dysregulation, and should be further studied in physiological conditions in cellular and animal models expressing mitoTRPV1 endogenously.
SN - 1420-682X
SN - 1420-9071
ER -