ROLE OF CHAPERONES IN THE BIOGENESIS AND MAINTENANCE OF THE MITOCHONDRION

All cells depend on correctly folded proteins for optimal function. A central question in cellular biology is how such folded structures are formed and maintained, a process that is now recognized to rely heavi ly on a group of proteins called molecular chaperones. Molecular chape rones constitute distinct families of proteins that are ubiquitous and highly conserved from bacteria to humans, They appear to bind nonnati ve conformations of most, if not all, proteins, thereby preventing the ir aggregation and subsequent inactivation. The chaperones not only pr otect newly synthesized proteins during transport and folding, but als o serve to maintain the cell in a healthy state during exposure to a m ultitude of stress conditions. Accordingly, chaperones are expressed c onstitutively, but their synthesis is further enhanced during stress c onditions. Detailed insights into the role of molecular chaperones hav e come from studies of mitochondrial protein biogenesis, a process in which chaperones act as unfoldases, pulling devices, and foldases. In this review we summarize these developments and further discuss the po tential role of chaperones in mitochondrial DNA metabolism and human m itochondrial disease states.