The multiple facets of mitochondrial regulations controlling cellular thermogenesis

Understanding temperature production and regulation in endotherm organisms becomes a crucial challenge facing the increased frequency and intensity of heat strokes related to global warming. Mitochondria, located at the crossroad of metabolism, respiration, Ca²⁺ homeostasis, and apoptosis, were recently proposed to further act as cellular radiators, with an estimated inner temperature reaching 50 °C in common cell lines. This inner thermogenesis might be further exacerbated in organs devoted to produce consistent efforts as muscles, or heat as brown adipose tissue, in response to acute solicitations. Consequently, pathways promoting respiratory chain uncoupling and mitochondrial activity, such as Ca²⁺ fluxes, uncoupling proteins, futile cycling, and substrate supplies, provide the main processes controlling heat production and cell temperature. The mitochondrial thermogenesis might be further amplified by cytoplasmic mechanisms promoting the over-consumption of ATP pools. Considering these new thermic paradigms, we discuss here all conventional wisdoms linking mitochondrial functions to cellular thermogenesis in different physiological conditions.