Wijewantha, N. V., Kumar, R., & Nazarko, T. Y. (2024). Glycogen Granules Are Degraded by Non-Selective Autophagy in Nitrogen-Starved Komagataella phaffii. Cells, 13(6), 467.
Wijewantha, N. V., Kumar, R., & Nazarko, T. Y. (2024). Glycogen Granules Are Degraded by Non-Selective Autophagy in Nitrogen-Starved Komagataella phaffii. Cells, 13(6), 467.
Wijewantha, N. V., Kumar, R., & Nazarko, T. Y. (2024). Glycogen Granules Are Degraded by Non-Selective Autophagy in Nitrogen-Starved Komagataella phaffii. Cells, 13(6), 467.
Wijewantha, N. V., Kumar, R., & Nazarko, T. Y. (2024). Glycogen Granules Are Degraded by Non-Selective Autophagy in Nitrogen-Starved Komagataella phaffii. Cells, 13(6), 467.
Abstract
Autophagy was initially recognized as a bulk degradation process that randomly sequesters and degrades cytoplasmic material in lysosomes (vacuoles in yeast). In recent years, various selective autophagy pathways have been discovered. Glycophagy, the selective autophagy of glycogen granules, is one of them. It is an important contributor to Pompe disease, a type of lysosomal storage disorder with lysosomal accumulation of glycogen. Here, we developed the Komagataella phaffii yeast as a simple model of glycogen autophagy under nitrogen starvation conditions. For this, we turned the self-glucosylating initiator of glycogen synthesis, Glg1, which is covalently bound to glycogen, into the Glg1-GFP autophagic reporter. Our results revealed that vacuolar delivery of Glg1-GFP and its processing to free GFP were strictly dependent on autophagic machinery and vacuolar proteolysis. Notably, this process was independent of Atg11, the scaffold protein common for many selective autophagy pathways. Importantly, the non-mutated Glg1-GFP (which synthesizes and marks glycogen) and mutated Glg1Y212F-GFP (which does not synthesize glycogen and is degraded by non-selective autophagy as cytosolic Pgk1-GFP) were equally well delivered to the vacuole and had similar levels of released GFP. Therefore, we concluded that glycogen autophagy is a non-selective process in K. phaffii yeast under nitrogen starvation conditions.
Biology and Life Sciences, Cell and Developmental Biology
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