Peroxisome deficiency impacts metabolites of lysine, lipid, and polyamine metabolism in Saccharomyces cerevisiae.

Peroxisomes are eukaryotic organelles primarily known for their conserved roles in fatty acid β-oxidation and hydrogen peroxide detoxification. These organelles are also involved in a diverse range of other metabolic and non-metabolic functions. We recently compared the transcriptome and proteome of Saccharomyces cerevisiae wild-type and peroxisome-deficient (pex3) cells. This study uncovered the major processes and metabolic pathways that are influenced by peroxisomes. Here we performed a mass spectrometry-based analysis of intracellular metabolites of the same two strains. This led to the identification of 160 compounds, of which seven exhibited significant differences between wild-type and pex3 cells (glycerol-3-phosphate, carnitine, pantothenate, acetyl-spermidine, propionyl-carnitine, and aminolevulinic acid). Notably, we observed elevated lysine levels in pex3 cells, consistent with previous findings, which confirms the reliability and accuracy of our analytical approach. In addition, changes in carnitine compounds were measured, aligning with the proposed occurrence of a carnitine shuttle across the peroxisomal membrane. By integration of the current metabolomic data with the previously obtained transcriptomic and proteomic data, we provide a broader view of the metabolic impact of peroxisome deficiency. We show that, in addition to the well-known function of yeast peroxisomes in lipid and fatty acid degradation, these organelles are also involved in lipid synthesis. Furthermore, our study revealed that peroxisome deficiency affects polyamine homeostasis.