Assembly of β-barrel proteins in the mitochondrial outer membrane

• Mitochondrial β-barrel proteins descend from bacterial outer membrane proteins.
• β-Barrel membrane protein biogenesis in mitochondria depends on the SAM complex.
• The β-signal in the C-terminal β-strand is recognized by the SAM complex.
• The core protein Sam50 is an evolutionary conserved β-barrel membrane protein.
• The formation of mitochondrial membrane contact sites depends on SAM subunits.

Mitochondria evolved through endosymbiosis of a Gram-negative progenitor with a host cell to generate eukaryotes. Therefore, the outer membrane of mitochondria and Gram-negative bacteria contain pore proteins with β-barrel topology. After synthesis in the cytosol, β-barrel precursor proteins are first transported into the mitochondrial intermembrane space. Folding and membrane integration of β-barrel proteins depend on the mitochondrial sorting and assembly machinery (SAM) located in the outer membrane, which is related to the β-barrel assembly machinery (BAM) in bacteria. The SAM complex recognizes β-barrel proteins by a β-signal in the C-terminal β-strand that is required to initiate β-barrel protein insertion into the outer membrane. In addition, the SAM complex is crucial to form membrane contacts with the inner mitochondrial membrane by interacting with the mitochondrial contact site and cristae organizing system (MICOS) and shares a subunit with the endoplasmic reticulum–mitochondria encounter structure (ERMES) that links the outer mitochondrial membrane to the endoplasmic reticulum (ER).