title: Swapping of the N-terminus of VDAC1 with VDAC3 restores full activity of the channel and confers anti-aging features to the cell.
abstract: Voltage-dependent anion-selective channels (VDACs) are pore-forming proteins allowing the permeability of the mitochondrial outer membrane. The VDAC3 isoform is the least abundant and least active in a complementation assay performed in a yeast strain devoid of porin-1. We swapped the VDAC3 N-terminal 20 amino acids with homologous sequences from the other isoforms. The substitution of the VDAC3 N-terminus with the VDAC1 N-terminus caused the chimaera to become more active than VDAC1. The VDAC2 N-terminus improved VDAC3 activity, though to a lesser extent. The VDAC3 carrying the VDAC1 N-terminus was able to complement the lack of the yeast porin in mitochondrial respiration and in modulation of reactive oxygen species (ROS). This chimaera increased life span, indicating a more efficient bioenergetic metabolism and/or a better protection from ROS.
authors.affiliation: Department of Chemical Sciences, University of Catania, Catania, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Reina
authors.forename: Vanessa
authors.initials: V
authors.lastname: Palermo
authors.forename: Andrea
authors.initials: A
authors.lastname: Guarnera
authors.forename: Francesca
authors.initials: F
authors.lastname: Guarino
authors.forename: Angela
authors.initials: A
authors.lastname: Messina
authors.forename: Cristina
authors.initials: C
authors.lastname: Mazzoni
authors.forename: Vito
authors.initials: V
authors.lastname: De Pinto
mesh_terms: D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D033681:Mitochondrial Membrane Transport Proteins; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D050995:Voltage-Dependent Anion Channel 1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D050994:Voltage-Dependent Anion Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; C494762:VDAC1 protein, human; C494768:VDAC3 protein, human; D050994:Voltage-Dependent Anion Channels; D006861:Hydrogen Peroxide; D050995:Voltage-Dependent Anion Channel 1