Trends Cell Biol. 2019;29(7):534-548

Trends Cell Biol.                  online article

Mitochondria import about 1000 proteins, which are produced as precursors on cytosolic ribosomes. The translocase of the outer mitochondrial membrane (TOM complex) forms the entry gate for almost all mitochondrial precursor proteins. Subsequently, dedicated protein translocases of the two surrounding membranes mediate the transport of these preproteins to the mitochondrial subcompartments. While protein sorting within mitochondria is understood to some detail, only little is known how precursor proteins are transferred to the mitochondrial surface. In this review, we summarize the major targeting pathways for precursor proteins to mitochondria. A co-translational import mechanism was reported for a fraction of mitochondrial precursor proteins. In the post-translational import mode,   different cytosolic chaperones guide specific subsets of preproteins to the TOM receptors. Finally, a close cross-talk to protein targeting pathways to other cell organelles like the endoplasmic reticulum have been reported. Altogether, a complicated network of targeting factors and pathways mediate and control transport preproteins to the mitochondrial surface.