Heatshock

Heat shock refers to exposure to elevated temperatures that disrupt cellular proteostasis. In many organisms, such stress triggers a conserved transcriptional program called the heat shock response (HSR), which upregulates a group of proteins known as heat shock proteins (HSPs). HSPs function as molecular chaperones and are involved in protein folding, prevention of aggregation, and, when needed, targeted degradation of damaged proteins.

The regulatory circuitry of the heat shock response varies by domain of life. In bacteria, the response is governed mainly by the sigma factor σ32 (RpoH), which increases transcription of chaperones such as DnaK, DnaJ, and GrpE. In eukaryotes, heat shock transcription factors (e.g., HSF1 in animals, HsfA1 in plants) sense proteotoxic stress; they trimerize, translocate to the nucleus, bind heat shock elements in DNA, and induce expression of HSPs such as HSP70, HSP90, HSP60, and small HSPs. Feedback mechanisms, including binding of HSPs to the transcription factors, help shut off the response when homeostasis is restored.

The primary outcome of the heat shock response is enhanced proteostasis: increased capacity to refold denatured proteins, prevent aggregation, and mediate degradation of severely damaged proteins. This can confer acquired thermotolerance, where a prior mild heat exposure improves survival under subsequent heat stress.

Heat shock responses are broadly conserved across bacteria, archaea, plants, and animals and can be triggered by other forms of proteotoxic stress, such as oxidative stress or toxins. The concept is widely used in research on stress physiology, aging, neurodegenerative disease, and cancer biology.