Connection of Protein Transport and Organelle Contact Sites in Mitochondria

Mitochondrial biogenesis and function depend on the intensive exchange of molecules with other cellular compartments. The mitochondrial outer membrane plays a central role in this communication process. It is equipped with a number of specific protein machineries that enable the transport of proteins and metabolites. Furthermore, the outer membrane forms molecular contact sites with other cell organelles like the endoplasmic reticulum (ER), thus integrating mitochondrial function in cellular physiology. The best-studied mitochondrial organelle contact site, the ER–mitochondria encounter structure (ERMES) has been linked to many vital processes including mitochondrial division, inheritance, mitophagy, and phospholipid transport. Strikingly, ER–mitochondria contact sites are closely connected to outer membrane protein translocases. The translocase of the outer mitochondrial membrane (TOM) represents the general mitochondrial entry gate for precursor proteins that are synthesized on cytosolic ribosomes. The outer membrane also harbors the sorting and assembly machinery (SAM) that mediates membrane insertion of β-barrel proteins. Both of these essential protein translocases are functionally linked to ER–mitochondria contact sites. First, the SAM complex associates with an ERMES core component to promote assembly of the TOM complex. Second, several TOM components have been co-opted as ER–mitochondria tethers. We propose that protein import and organelle contact sites are linked to coordinate processes important for mitochondrial biogenesis.