Phosphate transport in mitochondria: past accomplishments, present problems, and future challenges.

The requirement of inorganic phosphate (Pi) for oxidative phosphorylation in eukaryotic cells is fulfilled through specific Pi transport systems. The mitochondrial proton/phosphate symporter (Pic) is a membrane-embedded protein which translocates Pi from the cytosol into the mitochondrial matrix. Pic is responsible for the very rapid transport of most of the Pi used in ATP synthesis. During the past five years there have been advances on several fronts. Genomic and cDNA clones for yeast, bovine, rat, and human Pic have been isolated and sequenced. Functional expression of yeast Pic in yeast strains deficient in Pi transport and expression in Escherichia coli of a chimera protein involving Pic and ATP synthase alpha subunit have been accomplished. Pic, in contrast to other members of the family of transporters involved in energy metabolism, was demonstrated to have a presequence, which optimizes the import of the precursor protein into mitochondria. Six transmembrane segments appear to be a structural feature shared between Pic and other mitochondrial anion carriers, and recent-site directed mutagenesis studies implicate structure-functional relationships to bacteriorhodopsin. These recent advances on Pic will be assessed in light of a more global interpretation of transport mechanism across the inner mitochondrial membrane.