Abstract
Zinc is an essential nutrient for all forms of life. Within cells, most zinc is bound to protein. Because zinc serves as a catalytic or structural cofactor for many proteins, cells must maintain zinc homeostasis under severely zinc-deficient conditions. In yeast, the transcription factor Zap1 controls the expression of genes required for uptake and mobilization of zinc, but to date the fate of existing zinc-binding proteins under zinc starvation remains poorly understood. Autophagy is an evolutionarily conserved cellular degradation/recycling process in which cytoplasmic proteins and organelles are sequestered for degradation in the vacuole/lysosome. In this study, we investigated how autophagy functions under zinc starvation. Zinc depletion induced non-selective autophagy, which is important for zinc-limited growth. Induction of autophagy by zinc starvation was not directly related to transcriptional activation of Zap1. Instead, TORC1 inactivation directed zinc starvation-induced autophagy. Abundant zinc proteins, such as Adh1, Fba1, and ribosomal protein Rpl37, were degraded in an autophagy-dependent manner. But the targets of autophagy were not restricted to zinc-binding proteins. When cellular zinc is severely depleted, this non-selective autophagy plays a role in releasing zinc from the degraded proteins and recycling zinc for other essential purposes.
Highlights
Zinc is an essential nutrient for all forms of life
As zinc starvation continued (Ͼ15 h), cell growth of atg2⌬ cells began to slow further, and these cells plateaued at a lower density (Fig. 1A), suggesting that autophagy plays an important role in supporting growth under zinc-depleted conditions
As cells are exposed to zinc starvation, Zap1 activates expression of genes needed for zinc uptake and mobilization of zinc from the vacuole
Summary
When cellular zinc is severely depleted, this non-selective autophagy plays a role in releasing zinc from the degraded proteins and recycling zinc for other essential purposes. Bulk degradation via autophagy is principally a non-selective process, selective targeting of proteins and organelles by autophagy plays important roles in cellular physiology [5]. Other forms of nutrient starvation or stress might invoke autophagy, but the mechanism and physiological roles of these diverse nutritional perturbations remain elusive. Transition metal ions such as iron, copper, zinc, and manganese are essential for life in all organisms. We investigated the function of autophagy under zinc starvation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
