Modulation of yeast transporter gene expression and lipid metabolism by hormesis mimicking calorie restriction

Abstract:

[Objective] Hydrogen peroxide-mediated ‘mitohormesis’ can mimic calorie restriction to extend yeast lifespan, but whether both share common mechanisms remains unknown. [Methods] Yeast chronological lifespan was determined by time-course colony counting. The fluctuations of ATP-binding cassette transporter gene expression profiles and lipid metabolism modes were analyzed by microarray chips. The dynamic changes of superoxide dismutase activities were compared by enzymatic assays. [Results] After treatment by calorie restriction, hydrogen peroxide or artesunate, yeast chronological lifespan was prolonged. Cellular detoxification-related transporter genes were downregulated or unchanged, whereas long-chain fatty acid transport-enhanced peroxisomal transporter genes as well as sterol uptake-accelerated plasma membrane transporter genes were upregulated. Accordingly, genes for lipid degradation such as the β-oxidation of fatty acids were upregulated, whereas genes for lipid synthesis including the extension and unsaturation of fatty acids were downregulated. Among different treatment groups, increase of Mn-SOD activity for mitochondrial hydrogen peroxide generation led to upregulation of antioxidant enzyme genes for hydrogen peroxide degradation and conversion. [Conclusion] Hormesis and calorie restriction exerting longevity-promoting effects depend not only on antioxidant enzymes-catalyzed reactions for scavenging reactive oxygen species, but also on ATP-binding cassette transporters-mediated lipid transport and subsequent lipid degradation and reutilization.