ER-phagy responses in yeast, plants, and mammalian cells and their crosstalk with UPR and ERAD

Abstract

ER-phagy, literally endoplasmic reticulum (ER)-eating, defines the constitutive or regulated clearance of ER portions within metazoan endolysosomes or yeast and plant vacuoles. The advent of electron microscopy led to the first observations of ER-phagy over 60 years ago, but only recently, with the discovery of a set of regulatory proteins named ER-phagy receptors, has it been dissected mechanistically. ER-phagy receptors are activated by a variety of pleiotropic and ER-centric stimuli. They promote ER fragmentation and engage luminal, membrane-bound, and cytosolic factors, eventually driving lysosomal clearance of select ER domains along with their content. After short historical notes, this review introduces the concept of ER-phagy responses (ERPRs). ERPRs ensure lysosomal clearance of ER portions expendable during nutrient shortage, nonfunctional, present in excess, or containing misfolded proteins. They cooperate with unfolded protein responses (UPRs) and with ER-associated degradation (ERAD) in determining ER size, function, and homeostasis.

Keywords: ER-associated degradation (ERAD); ER-phagy; ER-phagy response (ERPR); ER-to-lysosome-associated; autophagosome; autophagy; degradation (ERLAD); endolysosome; lysosome; recov-ER-phagy; unfolded proteins response (UPR); vacuole.