Interplay between the endoplasmic reticulum and cellular homeostasis

Abstract

Autophagy and endoplasmic reticulum-associated protein degradation (ERAD) are stress response pathways required for cell homeostasis. These two clearance pathways involve the trafficking and degradation of cellular components. Autophagy is characterized by the engulfment of the targeted cargo by cytosolic double membrane vesicles: autophagosomes. Our group has identified the Saccharomyces cerevisiae ER-localized Qa-SNARE Ufe1p, as a novel component, needed in autophagy. In ufe1-1 cells expressing GFP-Atg8, there is no generation of free GFP at the non-permissive temperature, indicating impairment in the autophagic flux. Furthermore, the analysis of the electron microscopy images of this conditional mutant strain revealed a significant reduction in number and size of autophagosomes. Moreover, the number of autophagic bodies is almost absent in this mutant. Together, these results indicate that Ufe1p plays a role in autophagosome biogenesis and autophagy flux. Furthermore, we investigate the degradation mechanisms of post-translational modified misfolded proteins by ERAD. Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are secretory proteins anchored to the luminal leaflet of the ER membrane. It has been recently enquired whether GPI-APs may be refractory to degradation by ERAD because of their covalently attached glycolipid, which might poses a topologic hindrance for ERAD. We have demonstrated that the yeast misfolded GPI-AP, Gas1*p, it is indeed degraded by ERAD when GPI remodeling or ER export of the GPI-APs are compromised. Additional mechanisms might also be implicated in its turnover, like autophagy.