Transfer of nuclear proteins to mitochondria--a role in mitochondrial disease.

Abstract

Of the hundreds of proteins localized to mitochondria, only thirteen (in man) are encoded by the mitochondrial genome and synthesized within the mitochondria. All of the rest are encoded in the nucleus and synthesized on cytoplasmic ribosomes and must be translocated into mitochondria before they can carry out their structural and catalytic functions. Most of these are synthesized as larger precursor proteins with amino-terminal extensions called leader peptides that target them to mitochondria; the leader peptides are then proteolytically removed after translocation is complete. The details of this pathway have been worked out in yeast, Neurospora, and mammals and are remarkably conserved across this range of organisms. Our current understanding of this process can be summarized as in the diagram below: