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. Budding yeast mRNA-enriched profiles from 42 individual samples of prototrophic BY4741 cells, including 3 replicates of 7 time points and 2 treatments (control and drug-treated). Additionally 2 different mixes of ERRC spike-in RNA controls were added to the samples; one mix for the control samples, and one mix for the drug-treated samples.