Early Events in Protein Import into Mitochondria

Abstract

Assembly of newly synthesized precursor proteins into mitochondria involves events occurring both in the cytosol and at the surface of the organelle. Co-incident with or shortly following protein translation, recognition events must take place to allow a precursor to be correctly targeted to its final destination (Pfanner and Neupert, 1990; Glick and Schatz 1991). Cellular recognition of specific structural features of mitochondrial proteins takes several forms Structural information must be recognized that specifies the destination of the protein, such as that contained in amino terminal pre-sequences that are sufficient to direct even foreign proteins to mitochondrial locations. In addition to this “positive” targeting information, the cell must recognize “negative” targeting information, i.e., properties of a protein which might impair its ability to be correctly localized. To be more specific, a precursor must be prevented from aggregating or assuming a tightly folded conformation that cannot be translocated linearly through a small diameter membrane channel (Rassow et al., 1990). Recognition of “positive” targeting information is the job of the receptors and translocation apparatus on the surface of the mitochondria (Pfanner et al., 1991). Recognition of “negative ” targeting information, i.e. the maintenance of a “transport-competent” conformation, is the work of cytoplasmic protein chaperones such as hsp70 (Deshaies et al., 1988). In neither case are the molecular details well understood. In this paper we will describe work addressing both systems.