Heat shock proteins in protein folding and reactivation

Throughout their lives, cells synthesise new and dispose of the old, denatured proteins and insoluble protein aggregates. An important role in maintaining proteostasis is played by chaperones, which fold various proteins and promote degradation of denatured or misfolded proteins via proteasomes or autophagy. Despite protein folding being an accurate process, as organisms age and experience stress, errors accumulate, which leads to the formation of protein aggregates that can result in pathological changes. In addition, stress factors such as elevated temperature and altered pH can promote protein denaturation that can result in the proteins not only losing their native functions, but also gaining novel cytotoxic properties. With the increase of human average lifespan, more and more cases of proteinopathies – diseases caused by disruptions in proteostasis, e. g. Alzheimer’s disease, Huntington’s disease etc. – emerge. Therefore, identification of mechanisms preventing the formation of cytotoxic protein aggregates and promoting their clearance is of high importance. Heat shock proteins (HSPs) are the molecular chaperones involved in folding nascent proteins and refolding the denatured ones, leading to their reactivation. Heat shock proteins vary in structure and functions and are found in all prokaryotes and eukaryotes discovered to date. HSPs are constantly synthesised in cells under normal conditions, and a multitude of them are dramatically up-regulated during stress, which includes heat shock (which earned them their name) and metabolic stress caused by the increased numbers of misfolded proteins. In this review, we describe mechanisms of action and functions of members of five heat shock protein families.