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Ongay-Larios, Laura, Kawasaki, Laura, Vincent, Olivier, Coello, Gerardo, Coria, Roberto, Escalante, Ricardo, Dominguez-Martin, Eunice, (2018) ' IreA controls endoplasmic reticulum stress-induced autophagy and survival through homeostasis recovery. ' Mol. Cell. Biol.

 

Abstract:The Unfolded Protein Response (UPR) is an adaptive pathway that restores cellular homeostasis after endoplasmic reticulum (ER) stress. The ER-resident kinase/ribonuclease Ire1 is the only UPR sensor conserved during evolution. Autophagy, a lysosomal degradative pathway, also contributes to the recovery of cell homeostasis after ER-stress but the interplay between these two pathways is still poorly understood. We describe the Dictyostelium discoideum ER-stress response and characterize its single bonafide Ire1 orthologue, IreA. We found that tunicamycin (TN) triggers a gene-expression reprogramming that increases the protein folding capacity of the ER and alleviates ER protein load. Further, IreA is required for cell-survival after TN-induced ER-stress and is responsible for nearly 40% of the transcriptional changes induced by TN. The response of Dictyostelium cells to ER-stress involves the combined activation of an IreA-dependent gene expression program and the autophagy pathway. These two pathways are independently activated in response to ER-stress but, interestingly, autophagy requires IreA at a later stage for proper autophagosome formation. We propose that unresolved ER-stress in cells lacking IreA causes structural alterations of the ER, leading to a late-stage blockade of autophagy clearance. This unexpected functional link may critically affect eukaryotic cell survival under ER-stress.
Status:	aheadofprint	Type:	Journal article	Source:	PUBMED	PubMed ID:	29632077

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	Genes addressed in this paper
	DDB_G0276445	atg1	atg101	atg13	cdcD	ifkA	ifkB	ireA
Topics in this paper
Protein Physical Properties	X					X	X	X
Mammalian Gene Related	X					X	X	X
Protein Functional Domain								X
Strains/Constructs								X
Non-mammalian Gene Related								X
Cellular Location								X
Function/Process								X
Regulatory Role								X
Regulated By	X				X
Mutants/Phenotypes		X	X	X				X