Reduced sphingolipid biosynthesis modulates proteostasis networks to enhance longevity

Treating Saccharomyces cerevisiae cells with myriocin reduces the intracellular free pool of most amino acids. We find that transcriptional changes within the first 6 hours of drug treatment seem to have little impact on free pool changes. Rather the changes are driven early by post-translational events including impaired amino acid transporter activity, due to a reduced rate of sphingolipid biosynthesis, and an increased rate of endocytosis of at least some amino acid transporters, particularly the major methionine transporter Mup1.使用米里霉素（myriocin）处理酿酒酵母（Saccharomyces cerevisiae）细胞，可降低其细胞内大多数氨基酸的游离池水平。我们发现，药物处理最初6小时内的转录变化似乎对该游离池的变化影响极小；相反，此类变化早期由翻译后事件驱动，包括因鞘脂生物合成速率降低导致的氨基酸转运蛋白活性受损，以及至少部分氨基酸转运蛋白（尤其是主要甲硫氨酸转运蛋白Mup1）的内吞速率升高。