Glycogen is a neutral cargo of bulk autophagy in Komagataella phaffii.

Glycogen is a primary cellular energy store in numerous eukaryotes. Its biosynthesis is a main strategy to cope with forthcoming starvation. During starvation, glycogen is processed in the cytosol or delivered for degradation to animal lysosomes or yeast vacuoles by macroautophagy (hereafter autophagy). However, the mechanism of glycogen autophagy is poorly understood, especially in the heart and skeletal muscles that suffer from the lysosomal glycogen accumulation in Pompe disease. We recently developed the Komagataella phaffii yeast as a simple model to study glycogen autophagy and found that this pathway proceeds non-selectively. However, studies in Saccharomyces cerevisiae proposed glycogen as a non-preferred cargo of bulk autophagy. In our latest study with new fluorescent reporters for glycogen, we clarified cargo properties of K. phaffii glycogen. Both homologous and heterologous markers of glycogen are delivered to the vacuole and degraded with efficiencies that are independent of glycogen, suggesting that glycogen is a neutral cargo of bulk autophagy. This work provides insights into the evolutionary diversity of glycogen autophagy in yeasts with implications for understanding this process in complex eukaryotes.