Heat shock proteins (Hsp) are a family of highly conserved proteins that include both constitutively expressed (Hsp60, Hsp70, and Hsp90) and stress-induced (Hsp27 and Hsp72) proteins. Hsp60 is a mitochondrial protein that promotes protein folding and facilitates proteolytic degradation of misfolded or denatured proteins in the mitochondria. Hsp10 interacts with Hsp60 to regulate its substrate binding and ATPase activity. In HeLa and Jurkat mitochondria, Hsp60 associates with caspase-3 to form a complex that dissociates and releases from the mitochondria during apoptosis. Hsp60 accelerates the maturation of procaspase-3 through its ATP-dependent ''foldase activity. In addition to its protein folding activity, Hsp60 can bind the toll-like receptor-4 complex leading to production of TNFalpha and stimulation of a pro-inflammatory response in macrophages. Thus, the protein folding function of Hsp60 is involved in protein folding in both normal and apoptotic cells, while release of Hsp60 during necrosis is thought to stimulate a pro-inflammatory response.
