McDonnell, Samantha J, Spiller, David G, White, Michael RH, Prior, Ian A 
ORCID: 0000-0002-4055-5161 and Paraoan, Luminita ORCID: 0000-0001-7568-7116
(2019)
ER stress-linked autophagy stabilizes apoptosis effector PERP and triggers its co-localization with SERCA2b at ER-plasma membrane junctions.
CELL DEATH DISCOVERY, 5 (1).
132-.
Abstract
Specific molecular interactions that underpin the switch between ER stress-triggered autophagy-mediated cellular repair and cellular death by apoptosis are not characterized. This study reports the unexpected interaction elicited by ER stress between the plasma membrane (PM)-localized apoptosis effector PERP and the ER Ca<sup>2+</sup> pump SERCA2b. We show that the p53 effector PERP, which specifically induces apoptosis when expressed above a threshold level, has a heterogeneous distribution across the PM of un-stressed cells and is actively turned over by the lysosome. PERP is upregulated following sustained starvation-induced autophagy, which precedes the onset of apoptosis indicating that PERP protein levels are controlled by a lysosomal pathway that is sensitive to cellular physiological state. Furthermore, ER stress stabilizes PERP at the PM and induces its increasing co-localization with SERCA2b at ER-PM junctions. The findings highlight a novel crosstalk between pro-survival autophagy and pro-death apoptosis pathways and identify, for the first time, accumulation of an apoptosis effector to ER-PM junctions in response to ER stress.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Apoptosis, Lysosomes, Macroautophagy |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 16 Sep 2019 10:54 |
| Last Modified: | 19 Jan 2023 00:26 |
| DOI: | 10.1038/s41420-019-0212-4 |
| Open Access URL: | https://doi.org/10.1038/s41420-019-0212-4 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3054819 |
Dimensions
Dimensions
