SUL1 deficiency reduces PKA activity to increase replicative lifespan in yeast Saccharomyces cerevisiae
The process of sulfate uptake plays a crucial role in cellular metabolism and growth. SUL1, a plasma membrane transporter responsible for regulating the entry of extracellular sulfate in S. cerevisiae. Our previous work verified SUL1 as a fundamental gene involved in the regulation of lifespan. This study aimed to undertake a more comprehensive analysis of the role of SUL1 in regulating longevity. Our data showed that that sulfate transport is not required for the effect of SUL1 deletion on increased longevity. The SUL1 mutant demonstrates decreased functionality within the PKA signaling pathway, resulting in a variety of effects, such as increased stress-protective trehalose and glycogen, enhanced autophagy, elevated expression of stress response genes, and reduced expression of ribosomal genes. Concurrently, the observed increase in lifespan resulting from the deletion of SUL1 may be partially attributed to the stimulation of autophagy and MSN2-mediated transcriptional activity. The findings of this study provide additional evidence for the association between sulfate transporter and longevity, thereby identifying a novel potential intervention target for extending lifespan. Overall design: To investigate the mechanism by which SUL1 mutations extend lifespan, exponential phase cells from the SUL1 mutant and wild-type (WT) groups were harvested and subjected to total RNA extraction for the construction of mRNA libraries intended for sequencing analysis. The WT strain was utilized as a control group, with three biological replicates per group.