====== Reticulophagy ======

Selective [[degradation]] of the [[endoplasmic reticulum]] (ER; reticulophagy) is a type of [[autophagy]] involved in the removal of ER fragments. So far, [[amino acid]] starvation as well as ER stress have been described as inducers of reticulophagy, which in turn restores cellular energy levels and ER [[homeostasis]]. 

Zielke et al. explored the autophagy-inducing mechanisms that underlie the autophagic cell death (ACD)-triggering compound [[loperamide]] (LOP) in [[glioblastoma]] cells. Interestingly, LOP triggers the upregulation of the transcription factor [[ATF4]], which is accompanied by the induction of additional ER stress markers. Notably, knockout of ATF4 significantly attenuated LOP-induced autophagy and ACD. Functionally, LOP also specifically induces the engulfment of large ER fragments within autophagosomes and lysosomes as determined by electron and fluorescence microscopy. LOP-induced reticulophagy and cell death are predominantly mediated through the reticulophagy receptor RETREG1/FAM134B and, to a lesser extent, TEX264, confirming that reticulophagy receptors can promote ACD. Strikingly, apart from triggering LOP-induced autophagy and ACD, ATF4 is also required for LOP-induced reticulophagy. These observations highlight a key role for ATF4, RETREG1 and TEX264 in response to LOP-induced ER stress, reticulophagy and ACD, and establish a novel mechanistic link between ER stress and reticulophagy, with possible implications for additional models of drug-induced ER stress
((Zielke S, Kardo S, Zein L, Mari M, Covarrubias-Pinto A, Kinzler MN, Meyer N, Stolz A, Fulda S, Reggiori F, Kögel D, van Wijk SJL. ATF4 links ER stress with reticulophagy in glioblastoma cells. Autophagy. 2020 Oct 28:1-17. doi: 10.1080/15548627.2020.1827780. Epub ahead of print. PMID: 33111629.)).