Mitochondrial protein homeostasis: the cooperative roles of chaperones and proteases.

Mitochondria contain an endogenous set of chaperones and proteases that form a complex and functionally interconnected protein quality control system responsible for maintenance of mitochondrial enzyme content and function (protein homeostasis). Here the functional roles of the ATP-dependent protease Pim1/LON and the ClpB-type chaperone Hsp78, both members of the ubiquitous AAA+ (ATPases associated with a wide variety of cellular activities) protein family, are described and discussed in the context of protein homeostasis processes under normal and stress conditions. Particular emphasis is set on cooperative mechanisms of protein quality control components in the specific recognition of damaged polypeptides and their subsequent removal. The coordinated biochemical activities of both Hsp78 and Pim1/LON prevent the accumulation of toxic protein aggregates in mitochondria and thereby indirectly ensure survival of the eukaryotic cell.