Monitoring ferroptosis in vivo: Iron-driven volatile oxidized lipids as breath biomarkers
Ferroptosis, an iron-dependent cell death mechanism characterized by excessive lipid peroxidation, has been implicated in numerous human diseases and organ pathologies. However, current detection methods necessitate invasive tissue sampling to assess lipid peroxidation, making noninvasive detection of ferroptosis in human subjects extremely challenging. In this study, we employed oxidative volatolomics to comprehensively characterize the volatile oxidized lipids (VOLs) produced during ferroptosis. Polyunsaturated fatty acid-derived VOLs were generated via iron-dependent LPO and released extracellularly as ferroptosis progressed. These VOLs were specifically generated during hepatic ferroptosis in mouse models of acetaminophen-induced liver injury and metabolic dysfunction-associated steatohepatitis (MASH) and were also detectable in the exhaled breath of patients with MASH. Specific VOLs released upon iron-dependent LPO are potential markers of ferroptosis in vivo and may facilitate noninvasive monitoring of cellular health in humans.
Authors
- Naoya Toriu (ORCID: https://orcid.org/0000-0002-3712-6331)
- Hiroaki Terajima (ORCID: https://orcid.org/0000-0001-7938-6345)
- Shujiro Yazumi (ORCID: https://orcid.org/0000-0002-0683-0000)
- Yoshinori Katsumata (ORCID: https://orcid.org/0000-0001-5576-5789)
- Yuta Matsuoka (ORCID: https://orcid.org/0000-0001-9860-3851)
- Sidonia Fagarasan (ORCID: https://orcid.org/0000-0003-2086-6402)
- Rae Maeda
- Yuki Muramoto (ORCID: https://orcid.org/0000-0002-9363-2722)
- Masaki Tajima (ORCID: https://orcid.org/0000-0003-3407-0229)
- Rei Morikawa (ORCID: https://orcid.org/0000-0003-4200-8070)
- Kojiro Taura (ORCID: https://orcid.org/0000-0003-4164-3988)
- Nobuhiro Nakamoto (ORCID: https://orcid.org/0000-0001-5203-7444)
- Po–Sung Chu (ORCID: https://orcid.org/0000-0002-8687-2760)
- Motoko Yanagita (ORCID: https://orcid.org/0000-0002-0339-9008)
- Kohta Iguchi (ORCID: https://orcid.org/0009-0000-0910-4955)
- Gen Honjo
- Genki Ichihara (ORCID: https://orcid.org/0000-0002-5580-989X)
- Yuki Sugiura (ORCID: https://orcid.org/0000-0002-6983-8958)
- Ken Takahashi (ORCID: https://orcid.org/0000-0002-7310-2257)
- Tadayuki Kou (ORCID: https://orcid.org/0000-0001-6397-2446)
- Ken‐ichi Yamada (ORCID: https://orcid.org/0000-0003-2100-8477)
- Ryo Ito (ORCID: https://orcid.org/0009-0003-3935-6311)
- Kazuki Sato (ORCID: https://orcid.org/0000-0002-0586-1868)
- Hata Kazuhiro
Institutions
- Tokai University (JP)
- Kyushu University (JP)
- Keio University (JP)
- Kyoto University (JP)
- Thermo Fisher Scientific (Japan) (JP)
- Kyoto University Hospital (JP)
- RIKEN Center for Integrative Medical Sciences (JP)
- Kitano Hospital (JP)
Publication Details
- Journal
- Redox Biology
- Published
- 2025-09-02
- DOI
- https://doi.org/10.1016/j.redox.2025.103858
- Citations
- 4
- Primary Topic
- Ferroptosis and cancer prognosis
- Type
- article
- Field-Weighted Citation Impact
- 6.07