Related Experiment Video
Updated: Jun 6, 2026
04:01
Revealing the Ferroptotic Phenotype of Medulloblastoma
Published on: March 15, 2024
Proteostasis-driven redox adaptation in ferroptosis: the p62-Keap1-Nrf2 axis
Nilufer Ercin1, Merve Beker2, Nail Besli3
1Department of Medical Biology, Institute of Health Sciences, University of Health Sciences, Istanbul, Türkiye.
Progress in Biophysics and Molecular Biology
|June 4, 2026
Summary
Protein homeostasis, regulated by p62, influences ferroptosis, a cell death pathway. The p62-Keap1-Nrf2 axis links proteostasis to redox balance, impacting cell adaptation and survival.
Area of Science:
- Cell Biology
- Biochemistry
- Pathology
Background:
- Ferroptosis is an iron-dependent cell death marked by lipid peroxidation, implicated in diseases.
- Current ferroptosis research often overlooks protein homeostasis (proteostasis) disruptions.
- p62, a key adaptor protein, links proteostasis, autophagy, and redox signaling.
Purpose of the Study:
- To review and integrate findings on the p62-Keap1-Nrf2 pathway in ferroptosis.
- To emphasize the pathway's role in redox buffering, autophagy, and cellular stress adaptation.
- To propose a framework for understanding ferroptosis as a balance of multiple cellular processes.
Main Methods:
- Literature review and synthesis of existing research.
- Analysis of the p62-Keap1-Nrf2 signaling axis in cellular stress.
- Integration of proteostasis, redox balance, and ferroptosis mechanisms.
Main Results:
- Alterations in p62 turnover under stress link proteostasis to the Keap1-Nrf2 axis.
- The p62-Keap1-Nrf2 pathway modulates redox regulation and autophagic flux.
- This axis acts as a regulatory system, not a direct ferroptosis executioner.
Conclusions:
- The p62-Keap1-Nrf2 axis is a critical link between proteostasis and redox balance in ferroptosis.
- Ferroptosis arises from a dynamic interplay of proteostasis, redox capacity, iron, and lipid peroxidation.
- Understanding this balance offers new perspectives on ferroptosis-related pathologies.
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