iRhom pseudoproteases regulate ER stress-induced cell death through IP3 receptors and BCL-2.
Authors
Atakpa-Adaji, Peace
Yeh, Yi-Chun
Levet, Clémence
Muliyil, Sonia
Lu, Fangfang
Publication Date
2022-03-10Journal Title
Nat Commun
ISSN
2041-1723
Publisher
Springer Science and Business Media LLC
Volume
13
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Dulloo, I., Atakpa-Adaji, P., Yeh, Y., Levet, C., Muliyil, S., Lu, F., Taylor, C., & et al. (2022). iRhom pseudoproteases regulate ER stress-induced cell death through IP3 receptors and BCL-2.. Nat Commun, 13 (1) https://doi.org/10.1038/s41467-022-28930-4
Description
Funder: Human Frontier Science Program (HFSP); doi: https://doi.org/10.13039/501100000854
Funder: Chinese Scholarship Council - University of Oxford Scholarship: 201806240008
Abstract
The folding capacity of membrane and secretory proteins in the endoplasmic reticulum (ER) can be challenged by physiological and pathological perturbations, causing ER stress. If unresolved, this leads to cell death. We report a role for iRhom pseudoproteases in controlling apoptosis due to persistent ER stress. Loss of iRhoms causes cells to be resistant to ER stress-induced apoptosis. iRhom1 and iRhom2 interact with IP3 receptors, critical mediators of intracellular Ca2+ signalling, and regulate ER stress-induced transport of Ca2+ into mitochondria, a primary trigger of mitochondrial membrane depolarisation and cell death. iRhoms also bind to the anti-apoptotic regulator BCL-2, attenuating the inhibitory interaction between BCL-2 and IP3 receptors, which promotes ER Ca2+ release. The discovery of the participation of iRhoms in the control of ER stress-induced cell death further extends their potential pathological significance to include diseases dependent on protein misfolding and aggregation.
Keywords
Article, /631/80/86, /631/80/642/1463, /631/45/269/1146, /631/80/82, /13/1, /13/2, /13/51, /13/89, /13/95, /13/106, /13/109, /14/1, /14/19, /14/28, /64, /64/24, /14, /14/63, article
Sponsorship
Wellcome Trust (101844/Z/13/Z)
Identifiers
s41467-022-28930-4, 28930
External DOI: https://doi.org/10.1038/s41467-022-28930-4
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334846
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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