Figure 2.

Signalling cascades inducing reticulophagy upon ER stress. The transmembrane protein Ire1 (yeast and mammals), ATF6, and PERK (mammals) sense the accumulation of unfolded proteins and/or aggregates, and trigger a general transcriptional response that affect the levels of proteins involved in autophagy. These include Atg8 (signal mediated through Ire1/Hac1 and unidentified alternative pathways in yeast) and Atg12 (mediated by the PERK/eIF2α signalling cascade in mammals). The Atg12-Atg5 (Atg16) complex facilitates the lipidation of Atg8 and autophagy induction. Unknown signalling events in yeast, dependent or independent of the inhibition of the Tor kinase, promote Atg1 activation. Green arrows indicate an increase in protein levels. Question marks indicate signalling cascades that may exist but have not yet been characterized.