Hsp60 and Hsp70 Chaperones: Guardians of Mitochondrial Proteostasis

Most protein molecules are dynamic and marginally stable and therefore constantly at risk for acquiring misfolded conformations. Constant surveillance is required to preserve proteostasis. Maintenance of the mitochondrial proteome relies on a diverse set of molecular chaperones and proteases, which together form an interconnected network. An imbalance in mitochondrial proteostasis will result in the accumulation of damaged polypeptides, potentially leading to collapse of mitochondrial integrity. The Hsp60 and Hsp70 chaperone systems play a central role in the folding of matrix-localised proteins. In this article, we summarise major aspects of the molecular function of these nano-machines and their interplay with other matrix chaperones and proteases. Hsp60 and Hsp70 chaperone systems play a crucial role in the maintenance of mitochondrial proteostasis.Hsp60 and Hsp70 carry out various functions via interaction with a large number of extra-mitochondrial complexes.In addition to its critical role in protein import into the mitochondria, Hsp70 plays an important role in protein folding, disaggregation and degradation in the mitochondrial matrix.Hsp60 is an essential protein that plays a central role in protein-folding within the mitochondrial matrix.The Hsp60 reaction cycle differs from that of GroEL in its incorporation of a single-ring intermediate in the reaction cycle.