Temperature is an omnipresent factor impacting on many aspects of life. In bacteria and ectothermic eukaryotes, various thermosensors and temperature-controlled switches have been described, ranging from RNA thermometers controlling the heat shock response in prokaryotes to temperature-dependent sex determination in reptiles, likely controlled through protein phosphorylation. However, the impact of subtle changes of human core body temperature are only beginning to be acknowledged. In this review, we will discuss thermosensing mechanisms and their functional implications with a focus on mammalian cells, also in the context of disease conditions. We will point out open questions and possible future directions for this emerging research field, which, in addition to molecular-mechanistic insights, holds the potential for the development of new therapeutic approaches.
