Mechanisms and pathways of mitochondrial outer membrane protein biogenesis

Outer membrane proteins integrate mitochondria into the cellular environment. They warrant exchange of small molecules like metabolites and ions, transport proteins into mitochondria, form contact sites to other cellular organelles for lipid exchange, constitute a signaling platform for apoptosis and inflammation and mediate organelle fusion and fission. The outer membrane contains two types of integral membrane proteins. Proteins with a transmembrane beta-barrel structure and proteins with a single or multiple alpha-helical membrane spans. All outer membrane proteins are produced on cytosolic ribosomes and imported into the target organelle. Precursors of beta-barrel and alpha-helical proteins are transported into the outer membrane via distinct import routes. The translocase of the outer membrane (TOM complex) transports beta-barrel precursors across the outer membrane and the sorting and assembly machinery (SAM complex) inserts them into the target membrane. The mitochondrial import (MIM) complex constitutes the major integration site for alpha-helical embedded proteins. The import of some MIM-substrates involves TOM receptors, while others are imported in a TOM-independent manner. Remarkably, TOM, SAM and MIM complexes dynamically interact to import a large set of different proteins and to coordinate their assembly into protein complexes. Thus, protein import into the mitochondrial outer membrane involves a dynamic platform of protein translocases.

Automated summary

Outer membrane proteins play crucial roles in integrating mitochondria into the cellular environment, facilitating exchange of metabolites and ions, forming signaling platforms for apoptosis and inflammation, and mediating organelle fusion and fission. These proteins, produced by cytosolic ribosomes, are imported into the target organelle via distinct import routes.