Biogenesis of mitochondrial β-barrel membrane proteins

beta-barrel membrane proteins in the mitochondrial outer membrane are crucial for mediating the metabolite exchange between the cytosol and the mitochondrial intermembrane space. In addition, the beta-barrel membrane protein subunit Tom40 of the translocase of the outer membrane (TOM) is essential for the import of the vast majority of mitochondrial proteins encoded in the nucleus. The sorting and assembly machinery (SAM) in the outer membrane is required for the membrane insertion of mitochondrial beta-barrel proteins. The core subunit Sam50, which has been conserved from bacteria to humans, is itself a beta-barrel protein. The beta-strands of beta-barrel precursor proteins are assembled at the Sam50 lateral gate forming a Sam50-preprotein hybrid barrel. The assembled precursor beta-barrel is finally released into the outer mitochondrial membrane by displacement of the nascent beta-barrel, termed the beta-barrel switching mechanism. SAM forms supercomplexes with TOM and forms a mitochondrial outer-to-inner membrane contact site with the mitochondrial contact site and cristae organizing system (MICOS) of the inner membrane. SAM shares subunits with the ER-mitochondria encounter structure (ERMES), which forms a membrane contact site between the mitochondrial outer membrane and the endoplasmic reticulum. Therefore, beta-barrel membrane protein biogenesis is closely connected to general mitochondrial protein and lipid biogenesis and plays a central role in mitochondrial maintenance. Mitochondrial beta-barrel precursors are synthesized in the cytosol and imported by the translocase of the outer membrane (TOM). The sorting and assembly machinery (SAM) inserts beta-barrel membrane proteins from the intermembrane space into the outer membrane. The endosymbiotic origin of mitochondria explains the conservation of the membrane insertion mechanism and of the essential core subunit Sam50 from bacteria to humans. image