Direct Membrane Insertion of Voltage-dependent Anion-selective Channel Protein Catalyzed by Mitochondrial Tom20
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Insertion of newly synthesized proteins into or across the mitochondrial outer membrane is initiated by import receptors at the surface of the organelle. Typically, this interaction directs the precursor protein into a preprotein translocation pore, comprised of Tom40. Here, we show that a prominent beta-barrel channel protein spanning the outer membrane, human voltage- dependent anion-selective channel (VDAC), bypasses the requirement for the Tom40 translocation pore during biogenesis. Insertion of VDAC into the outer membrane is unaffected by plugging the translocation pore with a partially translocated matrix preprotein, and mitochondria containing a temperature-sensitive mutant of Tom40 insert VDAC at the nonpermissive temperature. Synthetic liposomes harboring the cytosolic domain of the human import receptor Tom20 efficiently insert newly synthesized VDAC, resulting in transbilayer transport of ATP. Therefore, Tom20 transforms newly synthesized cytosolic VDAC into a transmembrane channel that is fully integrated into the lipid bilayer.
Biogenesis of mitochondrial β-barrel membrane proteins.
Ganesan I, Busto J, Pfanner N, Wiedemann N FEBS Open Bio. 2024; 14(10):1595-1609.
PMID: 39343721 PMC: 11452307. DOI: 10.1002/2211-5463.13905.
Role of the Mitochondrial Protein Import Machinery and Protein Processing in Heart Disease.
Zhao F, Zou M Front Cardiovasc Med. 2021; 8():749756.
PMID: 34651031 PMC: 8505727. DOI: 10.3389/fcvm.2021.749756.
The Biogenesis Process of VDAC - From Early Cytosolic Events to Its Final Membrane Integration.
Moitra A, Rapaport D Front Physiol. 2021; 12:732742.
PMID: 34456757 PMC: 8388839. DOI: 10.3389/fphys.2021.732742.
Seira O, Kolehmainen K, Liu J, Streijger F, Haegert A, LeBihan S Sci Rep. 2021; 11(1):16359.
PMID: 34381166 PMC: 8357839. DOI: 10.1038/s41598-021-96003-5.
Structure, gating and interactions of the voltage-dependent anion channel.
Najbauer E, Becker S, Giller K, Zweckstetter M, Lange A, Steinem C Eur Biophys J. 2021; 50(2):159-172.
PMID: 33782728 PMC: 8071794. DOI: 10.1007/s00249-021-01515-7.