McDonnell, Samantha, Spiller, David ORCID: 0000-0003-2502-6787, White, Michael, Prior, Ian 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.
742882-.
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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 2+ 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 |
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Additional Information: | BioXiv pre-print doi:10.1101/742882 |
Uncontrolled Keywords: | Generic health relevance |
Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
Depositing User: | Symplectic Admin |
Date Deposited: | 29 Jun 2021 09:27 |
Last Modified: | 15 Mar 2024 03:05 |
DOI: | 10.1101/742882 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3128110 |