The Overexpression of Superoxide Dismutase 1 Restores Growth Defect in a Porin1-Less Yeast Strain and Improves Mitochondrial Metabolism

Abstract

Metabolic exchanges between cytosol and mitochondria are made possible by the presence of the pore-forming protein VDAC1 on the outer mitochondrial membrane [1-3]. VDAC1 is directly involved in ATP/ADP, glucose and ions transportation, calcium homeostasis and apoptosis regulation. Moreover, it shows high level of sequence conservation in all eukaryotes: the homologous por1 in yeast S. cerevisiae shows 70% of identity and similar functional properties [1]. Recent studies have highlighted the existence of a link between VDAC1 and SOD1 enzyme, the most important cytosolic defense against superoxide anion. In yeast, SOD1 is required to protect VDAC1 from oxidation but also from carbonylation induced by ROS [3]; in addition, yeast strains devoid of endogenous SOD1 show down-regulated VDAC1 and TOM40 levels, and VDAC shows a significantly less pronounced voltage dependence and conductance [4]. To unravel SOD1 metabolic role in relation to VDAC1-mediated metabolism, we expressed human SOD1 in yeast devoid of endogenous VDAC (Δpor1). While Δpor1 strain cannot grow in the presence of a not-fermentable carbon source, possibly due to altered mitochondria, our results indicates that the overexpression of hSOD1 in Δpor1 strain relieves the growth defect, suggesting that SOD1 participates in the mitochondrial metabolic intersection with the cytosol.Acknowledgments: PRIN 2010CSJX4F (VDP) and ARISLA (AM).[1] Messina et al, 2012, BBA 1818, 1466-1476[2] De Pinto et al, 1989, BBA 987, 1-7[3] Tomasello et al, PlosOne, 2013, 8, e81522[4] O’Brien et al, 2004, JBC 279, 51817-51827[5] Karakitos et al, 2009, FEBS Lett 583, 449-455