Decoding Ferroptosis: Mechanistic Insights and Future Directions in the Precision Analysis of Lipid Hydroperoxides

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ID: 337600
2026
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Abstract
Abstract Ferroptosis is a regulated form of cell death driven by iron-dependent lipid peroxidation of polyunsaturated phospholipids. While its core regulatory axis involving glutathione peroxidase 4 (GPX4) and glutathione has been extensively studied, emerging evidence highlights the presence of multiple parallel defense systems. In addition, recent findings identify peroxiredoxin 6 as a critical regulator of intracellular selenium utilization, linking selenium metabolism to GPX4 biosynthesis and ferroptosis sensitivity. Despite these advances, a comprehensive understanding of ferroptosis mechanisms requires precise characterization of lipid hydroperoxides, the primary executioners of this cell death pathway. Here, we review the molecular basis of ferroptosis and its multilayered defense networks, with a particular focus on analytical challenges in lipid peroxidation research. We highlight recent progress in mass spectrometry–based approaches, including alkali metal adduction strategies, which enable positional isomer–resolved analysis of lipid hydroperoxides.
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openalex_W7224091423 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Junya Ito
Journal bioscience biotechnology and biochemistry
Year 2026
DOI
10.1093/bbb/zbag161
URL
https://doi.org/10.1093/bbb/zbag161
Keywords Keywords not found

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