Mitochondrial protein transport: Versatility of translocases and mechanisms

Biogenesis of mitochondria requires the import of approximately 1,000 different precursor proteins into and across the mitochondrial membranes. Mitochondria exhibit a wide variety of mechanisms and machineries for the translocation and sorting of precursor proteins. Five major import pathways that transport proteins to their functional intramitochondrial destination have been elucidated; these pathways range from the clas-sical amino-terminal presequence-directed pathway to pathways using internal or even carboxy-terminal targeting signals in the precursors. Recent studies have provided important insights into the structural orga-nization of membrane-embedded preprotein translocases of mitochondria. A comparison of the different translocases reveals the existence of at least three fundamentally different mechanisms: two-pore-translo-case, b-barrel switching, and transport cavities open to the lipid bilayer. In addition, translocases are phys-ically engaged in dynamic interactions with respiratory chain complexes, metabolite transporters, quality control factors, and machineries controlling membrane morphology. Thus, mitochondrial preprotein translo-cases are integrated into multi-functional networks of mitochondrial and cellular machineries.

Automated summary

Biogenesis of mitochondria involves the import of numerous precursor proteins across the mitochondrial membranes. Different import pathways exist, ranging from presequence-directed pathway to pathways using internal or carboxy-terminal targeting signals. Recent studies have revealed the structural organization of membrane-embedded preprotein translocases and their dynamic interactions with other cellular machineries. These insights provide valuable knowledge about the mechanisms of mitochondrial protein import.