title: Overexpression of human SOD1 in VDAC1-less yeast restores mitochondrial functionality modulating beta-barrel outer membrane protein genes.
abstract: Cu/Zn Superoxide Dismutase (SOD1), the most important antioxidant defense against ROS in eukaryotic cells, localizes in cytosol and intermembrane space of mitochondria (IMS). Several evidences show a SOD1 intersection with both fermentative and respiratory metabolism. The Voltage Dependent Anion Channel (VDAC) is the main pore-forming protein in the mitochondrial outer membrane (MOM), and is considered the gatekeeper of mitochondrial metabolism. Saccharomyces cerevisiae lacking VDAC1 (Δpor1) is a very convenient model system, since it shows an impaired growth rate on non-fermentable carbon source. Transformation of Δpor1 yeast with human SOD1 completely restores the cell growth deficit in non-fermentative conditions and re-establishes the physiological levels of ROS, as well as the mitochondrial membrane potential. No similar result was found upon yeast SOD1 overexpression. A previous report highlighted the action of SOD1 as a transcription factor. Quantitative Real-Time PCR showed that β-barrel outer-membrane encoding-genes por2, tom40, sam50 are induced by hSOD1, but the same effect was not obtained in Δpor1Δpor2 yeast, indicating a crucial function for yVDAC2. Since the lack of VDAC1 in yeast can be considered a stress factor for the cell, hSOD1 could relieve it stimulating the expression of genes bringing to the recovery of the MOM function. Our results suggest a direct influence of SOD1 on VDAC.
authors.affiliation: BIOMETEC, Department of Biomedical and Biotechnological Sciences, University of Catania, Italy; National Institute for Biostructures and Biosystems, Section of Catania, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Magrì
authors.affiliation: BIOMETEC, Department of Biomedical and Biotechnological Sciences, University of Catania, Italy; National Institute for Biostructures and Biosystems, Section of Catania, Italy.
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Di Rosa
authors.affiliation: CNR Institute of Biostructures and Bioimaging, Catania, Italy.
authors.forename: Marianna Flora
authors.initials: MF
authors.lastname: Tomasello
authors.affiliation: BIOMETEC, Department of Biomedical and Biotechnological Sciences, University of Catania, Italy; National Institute for Biostructures and Biosystems, Section of Catania, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Guarino
authors.affiliation: BIOMETEC, Department of Biomedical and Biotechnological Sciences, University of Catania, Italy; National Institute for Biostructures and Biosystems, Section of Catania, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Reina
authors.affiliation: Department of Biological, Geological and Environmental Sciences, Section of Molecular Biology, University of Catania, Italy; National Institute for Biostructures and Biosystems, Section of Catania, Italy. Electronic address: mess@unict.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Messina
authors.affiliation: BIOMETEC, Department of Biomedical and Biotechnological Sciences, University of Catania, Italy; National Institute for Biostructures and Biosystems, Section of Catania, Italy. Electronic address: vdpbiofa@unict.it.
authors.forename: Vito
authors.initials: V
authors.lastname: De Pinto
mesh_terms: D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D006540:Herbicides / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015151:Immunoblotting; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D016877:Oxidants / Q000494:pharmacology; D010269:Paraquat / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014170:Transformation, Genetic; D050995:Voltage-Dependent Anion Channel 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D006540:Herbicides; D008565:Membrane Proteins; D016877:Oxidants; D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; D029701:Saccharomyces cerevisiae Proteins; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D050995:Voltage-Dependent Anion Channel 1; D010269:Paraquat
keywords: Gene expression; Mitochondria; S. cerevisiae; SOD1; VDAC; sam50; tom40