Influence of butyrate on processes related to autophagic metabolism in Saccharomyces cerevisiae cells
Autophagy, butyrate, dysfunction, oxidative stress, Saccharomyces cerevisiae.
Butyrate is a metabolite generated from the fermentation of dietary fibers by intestinal bacteria, and it can be utilized in various metabolic pathways of eukaryotic cells. Autophagy is one of the main intracellular degradation pathways, involving the removal of cytoplasmic components detrimental to cells. Dysfunctions in this pathway are correlated with the onset and progression of various pathologies, such as cancer and neurodegenerative diseases. This study aimed to evaluate the influence of butyrate on steps of the autophagic process using Saccharomyces cerevisiae cells deficient in proteins essential for autophagy maintenance (Δatg8, Δgcn4, and Δpep4). Analysis of butyrate toxicity in the control strain, assessed by growth curves and cell viability, demonstrated no toxic effect within concentrations ranging from 50μM to 200μM. In assays with mutant strains at a butyrate concentration of 100μM, cells from the Δgcn4 and Δpep4 strains exhibited reduced metabolic activity. Upon autophagy induction by nitrogen starvation, it was observed that after 4h, there was no alteration in cell viability with butyrate exposure. However, after 24h, the Δgcn4 and Δpep4 strains showed a reduction in cell viability, a behavior associated with an increased frequency of petite colonies and elevated levels of intracellular oxidation. It is concluded that, under normal conditions, butyrate is not cytotoxic, but under autophagy induction, the Δgcn4 and Δpep4 strains demonstrated lower tolerance to low-concentration butyrate exposure and increased oxidative stress.