Mitochondrial protein transport: Versatility of translocases and mechanisms

• Published in: Molecular cell 2023-03, Vol.83 (6), p.890-910
• Main Authors: Busch, Jakob D., Fielden, Laura F., Pfanner, Nikolaus, Wiedemann, Nils
• Format: Article
• Language: English
• Subjects: biogenesis; Carrier Proteins - metabolism; electron transport chain; lipid bilayers; metabolites; mitochondria; Mitochondria - genetics; Mitochondria - metabolism; Mitochondrial Membrane Transport Proteins - genetics; Mitochondrial Membrane Transport Proteins - metabolism; Mitochondrial Membranes - metabolism; mitochondrial proteins; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Protein Precursors - metabolism; Protein Transport; quality control
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2023.02.020

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 classical 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 organization 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-translocase, β-barrel switching, and transport cavities open to the lipid bilayer. In addition, translocases are physically engaged in dynamic interactions with respiratory chain complexes, metabolite transporters, quality control factors, and machineries controlling membrane morphology. Thus, mitochondrial preprotein translocases are integrated into multi-functional networks of mitochondrial and cellular machineries. Mitochondria import a large variety of proteins from the cytosol. Busch et al. discuss how recent structural and functional findings have revealed a diversity of molecular mechanisms of protein translocation and insertion into membranes. Furthermore, they review the integration of the protein translocation machineries into multi-functional mitochondrial and cellular networks.