Mitochondrial import: properties of precursor proteins

Abstract

Most mitochondrial proteins are synthesized in the cytoplasm as higher molecular weight precursors and must cross at least one membrane to reach their final destination. Amino-terminal extensions of the precursors, termed signal peptides, have been shown to contain the necessary targeting information. Although no consensus sequence has been determined for signal peptides, all peptides examined to date have been shown to have membrane surface-seeking properties. The evidence so far seems to be consistent with a model in which the precursor initially associates with the lipids of the outer membrane and uses this surface to enhance subsequent diffusion to the import apparatus, thus modulating the overall rate of import. Precursors must at least partially unfold during import, although the extent and mechanism of unfolding remain unclear. The major possible mechanisms of unfolding include spontaneous unfolding of the precursor after engaging the translocation apparatus, ATP-dependent unfolding by a cytosolic factor (possibly the 70-kilodalton heat-shock proteins), and unfolding on the lipid surface of the outer mitochondrial membrane. It is possible that different types of precursors may utilize one or all of these mechanisms, in accordance with their individual needs.