Abstract

Oxidative stress is one of the major environmental stresses that the fungal pathogenCandida albicansfrequently encounters. In view of the negative regulatory effect of Ume6 on autophagy inSaccharomyces cerevisiaeand the close link between autophagy and oxidative stress in mammals, we explored the regulatory effect of Ume6 on autophagy and oxidative stress inC. albicansin this study. Here, we identify the transcriptional regulator Ume6 as a key positive regulator of autophagy under oxidative stress conditions. Deletion ofUME6resulted in reduced autophagy levels under H2O2treatment, correlating with reduced transcriptional expression of core autophagy-related genes. AlthoughUME6deletion alone did not alter H2O2sensitivity, it significantly exacerbated the sensitivity of a catalase mutant, revealing a functional role for Ume6 in oxidative stress tolerance. Intriguingly, we discovered that 3-methyladenine (3-MA), a canonical autophagy inhibitor in other systems, acts as an autophagy activator inC. albicans, promoting Atg8 transport to the vacuole and enhancing autophagy levels. This 3-MA-induced autophagy alleviated oxidative stress damage, as evidenced by improved growth and protection of vacuolar membrane integrity in H2O2-treated cells. Furthermore, deletion ofUME6or nitrogen starvation reduced apoptosis under oxidative stress, including decreased Annexin-V binding, metacaspase activation, mitochondrial membrane depolarization, and mitochondrial cytochrome c release. This study uncovers the critical role of Ume6 in governing oxidative stress, autophagy, and apoptosis.