Mitochondrial thermogenesis regulates heat-shock response in the nucleus

Mitochondrial thermogenesis is a process in which heat is generated by mitochondrial respiration. In living organisms, the thermogenic mechanisms that maintain body temperature have been studied extensively in fat cells, with little knowledge on how mitochondrial heat may act beyond energy expenditure. Here, we highlighted exothermic oxygen reduction reaction (Delta Hf degrees = -285 kJ/mol) is the main source of the protonophore-induced mitochondrial thermogenesis and this heat was conducted to other cellular organelles, including the nuclei. As a result, mitochondrial heat that reached the nucleus initiated the classical heat shock response, including the formation of nuclear stress granules and localization of heat shock factor 1 to chromatin. Consequently, activated HSF1 increases gene expression associated with the response to thermal stress in mammalian cells. Our results illustrate heat generated within the cells as a potential source of mitochondrial-nucleus communication and expand our understanding of the biological functions of mitochondria in cell physiology. ### Competing Interest Statement The authors have declared no competing interest.