Mitochondrial Thermogenesis Can Trigger 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 highlight that the exothermic
oxygen reduction reaction (ΔHf°
= −286 kJ/mol) is the main source of the protonophore-induced
mitochondrial thermogenesis, and this heat is conducted to other cellular
organelles, including the nucleus. As a result, mitochondrial heat
that reached the nucleus initiated the classical heat shock response,
including the formation of nuclear stress granules and the localization
of heat shock factor 1 (HSF1) to chromatin. Consequently, activated
HSF1 increases the level of 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 mitochondria-nucleus
communication and expand our understanding of the biological functions
of mitochondria in cell physiology.