Dual Role of Transcription Factors Msn2 and Msn4 in Lysosomal Remodeling Under Glucose Starvation in Yeast

Abstract

Under stress conditions, the lysosome adapts its metabolic and autophagic processes. One way the lysosome accomplishes this is by regulating its proteome through the activation of transcription factor EB (TFEB). However, little is known about TFEB-independent lysosome adaptation. Here we show that yeast transcription factors Msn2 and Msn4 play a significant role in yeast lysosome (vacuole) remodeling during glucose starvation. We conducted glucose starvation assays on the vacuolar proteome and performed RT-pCR and Western blotting to analyze changes to vacuolar proteins at the transcriptional and translational levels. Our findings indicated that vacuole remodeling is selective. Downregulation of vacuole membrane proteins was due to ubiquitin-dependent degradation, while upregulation of vacuole lumenal enzymes and E3-ubiquitin enzymes was transcriptionally mediated. In a msn2msn4 knockout, this upregulation was significantly impaired. Our results characterize the Msn2/4 glucose starvation response pathway and open new avenues for TFEB-independent lysosome biogenesis and remodeling.