Multiple thermometers in mammalian cells: why do cells from homeothermic organisms need to measure temperature?

Mammalian cells activate survival signaling pathways and other protective mechanisms or induce apoptotic cell death in response to heat stress at temperatures beyond the range of those that they would ever be expected to encounter in vivo. Recent work has demonstrated that heat shock directly activates the apoptotic proteins Bax and Bak, suggesting that these polypeptides function as cellular thermometers in the mitochondrial apoptotic pathway. Here we review this and other heat-activated signaling pathways and propose a model that postulates that these "cellular thermometers" are not designed to sense physiologically irrelevant temperatures but rather to detect a general buildup of abnormal proteins in the cytosol and other cellular compartments.