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Yang, Y.* ; Peng, H. ; Meng, D.* ; Fa, Z.* ; Chen, Y.* ; Lin, X.* ; Schick, J.A. ; Jin, X.*

Stress management: How the endoplasmic reticulum mitigates protein misfolding and oxidative stress by the dual role of glutathione peroxidase 8.

Biomolecules 15, 847 - 847 (2025)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The endoplasmic reticulum mediates essential processes such as protein folding, transport, and post-translational modifications. Disruptions in endoplasmic reticulum function can lead to the accumulation of unfolded or misfolded proteins, initiating endoplasmic reticulum stress. This stress activates the unfolded protein response, a multifaceted signaling pathway aimed at restoring proteostasis, which is crucial for cellular survival and fate determination. This review summarizes the current knowledge of three major branches of the unfolded protein response: the IRE1, PERK, and ATF6 signaling pathways. A key novel component in endoplasmic reticulum stress adaptation is the redox-sensitive enzyme glutathione peroxidase 8 (GPX8), which plays a dual role in detoxifying hydrogen peroxide and supporting proper protein folding. By connecting unfolded protein response branches, GPX8 reduces oxidative damage while maintaining redox homeostasis, emphasizing its importance in endoplasmic reticulum stability. Furthermore, plant glutathione peroxidases exhibit parallel functions in endoplasmic reticulum redox homeostasis and unfolded protein response activation, highlighting the evolutionary conservation of this protective mechanism across kingdoms. Understanding the intricate relationship between GPX8, endoplasmic reticulum stress, and unfolded protein response signaling provides novel insights into therapeutic strategies for diseases characterized by protein folding defects and oxidative stress.
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Publication type Article: Journal article
Document type Review
Corresponding Author
Keywords endoplasmic reticulum; oxidative stress; reactive oxygen species; unfolded protein response; GPX8
ISSN (print) / ISBN 2218-273X
e-ISSN 2218-273X
Journal Biomolecules
Quellenangaben Volume: 15, Issue: 6, Pages: 847 - 847 Article Number: , Supplement: ,
Publisher MDPI
Publishing Place Basel
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Signaling and Translation (SAT)
Grants Innovation Platform for Academicians of Hainan Province