title: Direct membrane insertion of voltage-dependent anion-selective channel protein catalyzed by mitochondrial Tom20.
abstract: 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.
authors.affiliation: Department of Biochemistry, McGill University, Montreal, Quebec, Canada H3G 1Y6.
authors.forename: E
authors.initials: E
authors.lastname: Schleiff
authors.forename: J R
authors.initials: JR
authors.lastname: Silvius
authors.forename: G C
authors.initials: GC
authors.lastname: Shore
mesh_terms: D000818:Animals; D001692:Biological Transport; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000648:ultrastructure; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D018272:Porins / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface; D050994:Voltage-Dependent Anion Channels
chemical_list: D007473:Ion Channels; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D018272:Porins; D011956:Receptors, Cell Surface; C084008:TOMM20 protein, human; C489998:Tomm20 protein, rat; D050994:Voltage-Dependent Anion Channels