Mitochondrial presequences.

Abstract

The discovery that proteins imported from the cytoplasm into mitochondria are usually synthesized as larger precursors (Maccecchini et al., 1979) has focussed attention on the function of targeting sequences in mitochondrial biogenesis. AS protein sorting within a cell is being elucidated, it becomes clear that mitochondria utilize a unique mechanism for the specific targeting and uptake of their proteins from the cytoplasm. This review will briefly describe recent efforts to determine the physical basis for the function of mitochondrial targeting signals. It is now well established that mitochondrial presequences are amino-terminal, up to at least 70 residues long, and removed by one or two proteolytic steps inside the mitochondria (for review see Hay et al., 1984; Douglas et al., 1986). When mitochondrial presequences are fused to nonmitochondrial proteins by recombinant DNA methods, the resulting fusion proteins are usually specifically transported into mitochondria (for review see Hurt and van Loon, 1986; Schatz, 1987). Thus, mitochondrial presequences contain a mitochondrial targeting signal which can function with different “passenger” proteins. This signal can be as short as 12 amino acids (Hurt and van Loon, 1986). While it is premature to conclude that the “mature” part of a natural precursor protein lacks any targeting signals, the information contained within a mitochondrial presequence is nevertheless sufficient to transport an attached protein into mitochondria. By far the largest class of import signals directs proteins to the mitochondrial matrix space. Because of the large number of examples, these “matrix-targeting” sequences have been studied most extensively.