Svf1 regulates oxidative stress response and cell survival in yeast.
Jennifer Brace, David VanderWeele, Charles Rudin
Medical Oncology, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD, 21231, USA
Aberrant regulation of apoptosis contributes to the etiology of several diseases including cancer. We hypothesized that key features of mammalian cell death regulation may be conserved in relatively simple organisms such as Saccharomyces cerevisiae. We identified the yeast gene SVF1 in a screen for mutations that could be functionally complemented by exogenous expression of the human anti-apoptotic gene Bcl-xL. Anti-apoptotic Bcl-2 family members have been shown to promote redox stability through upregulation of antioxidant pathways in mammalian cells. Here we demonstrate that the Svf1 protein functions as a mediator of the yeast cell response to oxidative stress. Cells lacking SVF1 are hypersensitive to conditions associated with increased reactive oxygen species (ROS) generation, including Bax expression, cold stress, and acetate exposure, as well as to direct chemical precursors of ROS including hydrogen peroxide and menadione. Hypersensitivity to oxidative stress can be reversed by re-introduction of SVF1 or treatment with the antioxidant N-acetylcysteine. In addition, exogenous SVF1 expression in mammalian cells confers resistance to hydrogen peroxide exposure, similar to that conferred by overexpression of Bcl-xL. Given the extensive literature implicating ROS and oxidative stress in mammalian apoptotic control, analysis of the parallel regulatory system in yeast may provide new insight into central mechanisms of cell death regulation in mammalian cells.
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