Peroxisomes and lipid droplets are key organelles in lipid metabolism in yeast Saccharomyces cerevisiae. We studied the role of a peroxisomal membrane protein Pex11, which is involved in the proliferation of peroxisomes and affects the expression of glycolytic genes. Regarding lipid droplets, the involvement of candidate causative genes MKT1, PHO23, PIG1 and RML2 in neutral lipid accumulation was evaluated and additional genetic elements affecting neutral lipids were analyzed. Using membrane yeast two hybrid system and bimolecular fluorescence complementation, we revealed an interaction between the proteins Pex11 and a mitochondrial membrane protein, Mdm34. Additionally, using fluorescent markers for peroxisomes and mitochondria, we proved that this interaction established a protein tether PerMES (Peroxisome-ERMES) between mitochondria and peroxisomes. By measuring the expression level of genes encoding glycolytic enzymes, we demonstrate association between central carbon metabolism and lipid metabolism through PEX11 gene: the gene RLF2 enhances the expression of ENO1, encoding enolase, and this effect is dependent on the presence of functional PEX11. By performing allele swaps of candidate causative alleles between two strains accumulating different levels of neutral lipids, and by constructing deletion mutants of these genes in both strains, we proved the alleles PHO23AWRI, PIG1AWRI in RML2S288c as superior for neutral lipid accumulation. We revealed potential additional genetic elements of neutral lipid accumulation by backcrossing to both parental strains. Importantly, our research contributes to the understanding of the role of Pex11 in processes other than peroxisomal proliferation, and elucidates the genetic architecture of neutral lipid accumulation in S. cerevisiae.
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