Autophagy is a cellular process that degrades subcellular constituents, and is conserved from yeast to mammals. Although autophagy is believed to be essential for living cells, cells lacking Atg5 or Atg7 are healthy, suggesting that a non‐canonical degradation pathway exists to compensate for the lack of autophagy. In this study, we show that the budding yeast Saccharomyces cerevisiae, which lacks Atg5, undergoes bulk protein degradation using Golgi‐mediated structures to compensate for autophagy when treated with amphotericin B1, a polyene antifungal drug. We named this mechanism Golgi membrane‐associated degradation (GOMED) pathway. This process is driven by the disruption of PI(4)P‐dependent anterograde trafficking from the Golgi, and it also exists in Atg5‐deficient mammalian cells. Biologically, when an Atg5‐deficient β‐cell line and Atg7‐deficient β‐cells were cultured in glucose‐deprived medium, a disruption in the secretion of insulin granules from the Golgi occurred, and GOMED was induced to digest these (pro)insulin granules. In conclusion, GOMED is activated by the disruption of PI(4)P‐dependent anterograde trafficking in autophagy‐deficient yeast and mammalian cells.
A novel Golgi membrane‐associated degradation (GOMED) pathway is activated when PI(4)P‐dependent Golgi‐to‐plasma membrane anterograde trafficking is disrupted in autophagy‐deficient yeast and mammalian cells.
Upon blockage of anterograde trafficking, autophagy‐deficient yeast cells accumulate autophagosome‐like structures, autophagic cargo degradation products and vesicular, autophagic body‐like structures.
The observed membranous structures seem to derive from the Golgi.
We named this degradative pathway Golgi membrane‐associated degradation (GOMED).
The GOMED pathway also functions in Atg5‐deficient mammalian cells when Golgi‐to‐plasma membrane trafficking is disrupted.
In autophagy‐deficient β‐cells, the GOMED pathway functions to suppress insulin secretion by degrading unused insulin granules in response to low glucose abundance.
- Received September 30, 2015.
- Revision received July 13, 2016.
- Accepted July 14, 2016.
- © 2016 The Authors