Role of membrane contact sites in protein import into mitochondria
16.12.2014
Horvath SE, Rampelt H, Oeljeklaus S, Warscheid B, vanderLaan M, Pfanner N.
Protein Sci. 2015;24(3):277-97
Mitochondria are central hubs in cellular metabolism and signalling. They are equipped with more than 1,000 different proteins that localize to one of the four mitochondrial subcompartments: outer membrane, inner membrane, intermembrane space, and matrix. Up to 99% of these protein are encoded by nuclear genes and synthesized in the cytosol as percursor proteins with specific targeting information in their primary structure. The correct and efficient sorting of all these proteins to their final destination requires several multi-modular protein translocases that transport water-soluble protein across and insert hydrophobic proteins into the outer and inner mitochondrial membranes. We found that these sophisticated molecular machines do not act as separate entities, but closely cooperate with each other. A hotspot of the corporate activities of mitchondrial protein translocases are the sites of direct physical contact between both mitochondrial membranes. Different types of membrane contact sites can be distinguished in mitochondria that support the routing of different classes of precursor proteins to distinct locations within the organelle. We propose that highly dynamic protein complex networks across two membranes are responsible for the remarkable versatility and accuracy of mitochondrial protein sorting.
