3 Chaperoning Mitochondrial Biogenesis

Abstract

I. INTRODUCTION
The parallel development of powerful in vitro systems and of genetic approaches has allowed considerable progress in understanding the mechanisms of protein transport into various cellular compartments. It is becoming ever more evident that transport processes across different cellular membranes are based on similar principles. Polypeptide chains appear to traverse lipid bilayers through proteinaceous pores. Translocation requires a “translocation-competent,” rather unfolded conformation. As a consequence, proteins must be partially unfolded or kept in an unfolded conformation prior to the translocation event and must refold after crossing the lipid membrane bilayer. In recent years, increasing evidence was obtained that both represent assisted processes. Molecular chaperones, in many cases originally identified as heat shock proteins, modulate the folding state of polypeptide chains in different cellular compartments.

Mitochondria, which contain heat shock proteins of the hsp70 and hsp60 family, proved to be a useful model system to study the function of chaperone proteins in protein translocation and folding. Although mitochondria contain their own DNA and independent systems for replication and protein synthesis, only a few subunits of the oxidative phosphorylation system and, in some organisms, components mediating splicing and translation of mitochondrial mRNA are encoded by the mitochondrial genome (Grivell 1989). About 95% of the total mass of mitochondrial proteins are encoded in the nucleus. They are synthesized on cytosolic polyribosomes, many of them as precursor molecules with amino-terminal presequences containing the targeting information. Import can occur posttranslationally followed by sorting to the various sub-compartments of mitochondria, the outer and inner...