No abstract

Cell size and morphology are key adaptive features that influence almost all aspects of cellular physiology such as cell cycle and lipid metabolism. Here we report the role of a transcription factor Suppressor Phenotype of Ty elements insertion 10 (SPT10) of Saccharomyces cerevisiae in regulating cell cycle, cell size and lipid metabolism in concert, in addition to its defined role of histone gene expression. Morphological and biochemical analyses of spt10Δ strain show an abnormal cell size, cell cycle and lipid levels. The expression of Spt10p in spt10Δ strain helps the cell revert to typical wild-type phenotypes. SPT10 controls lipid metabolism by negatively regulating the expression of lipid biosynthetic genes, and positively regulating the expression of the lipid hydrolyzing genes. Spt10p helps in maintaining the cell size by regulating the amount of carbon flux into the phospholipid constituents of the cell membranes. On the contrary, storage lipids have no role in regulating the cell size. An exogenous supply of phosphatidic acid increases the cell size, proving the positive impact of the phospholipids on cell size modulation. SPT10 affects cell cycle, cell size and lipid metabolism by an orchestrated transcriptional regulation of the corresponding genes.

A recent study showed that deletion of the gene encoding the transcription regulator SuPpressor of Ty10 (SPT10) increases total phospholipids, and our previous study established a critical link between phospholipids and the mevalonate/ergosterol (MEV/ERG) pathway, which synthesises triterpenes. This study aims to use spt10Δ yeast to improve triterpene production. Though MEV/ERG pathway was highly expressed in spt10Δ yeast, results showed insufficient accumulation of key metabolites and also revealed massive endoplasmic reticulum (ER) degradation. We found a stable, massive ER structure when we overexpressed diacylglycerol kinase1 (DGK1 OE ) in spt10Δ yeast. Analyses of ER-stress and autophagy suggest that DGK1 OE in the spt10Δ strain decreased autophagy, resulting in increased MEV/ERG pathway activity. Heterologous expression of β-amyrin synthase showed significant production of the triterpene β-amyrin in DGK1 OE spt10Δ yeast. Overall, our study provides a strategic approach to improve triterpene production by increasing ER biogenesis while limiting ER degradation.

Aggrephagy is a selective autophagic degradation intracellular mechanism that clears toxic misfolded protein aggregates such as α‐synuclein. Here, we identify and demonstrate that the small molecule, XCT 790 alleviates α‐synuclein‐mediated adverse effects in a yeast model of proteotoxicity. XCT 790 induced general autophagy and also enhanced starvation‐induced autophagy. Mechanistically, we showed that XCT 790 clears toxic α‐synuclein aggregates in an autophagy‐dependent manner. Interestingly, XCT 790 did not demonstrate a synergistic effect on autophagy induction in the presence of another autophagy inducer such as 6‐Bio.