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体内铁死亡监测：铁驱动的挥发性氧化脂质作为呼吸生物标志物。

Monitoring ferroptosis in vivo: Iron-driven volatile oxidized lipids as breath biomarkers.

作者信息

Matsuoka Yuta, Katsumata Yoshinori, Chu Po-Sung, Morikawa Rei, Nakamoto Nobuhiro, Iguchi Kohta, Takahashi Ken, Kou Tadayuki, Ito Ryo, Taura Kojiro, Yazumi Shujiro, Terajima Hiroaki, Honjo Gen, Ichihara Genki, Muramoto Yuki, Sato Kazuki, Maeda Rae, Hata Kazuhiro, Toriu Naoya, Yanagita Motoko, Tajima Masaki, Fagarasan Sidonia, Yamada Ken-Ichi, Sugiura Yuki

机构信息

Multi-Omics Platform, Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan.

出版信息

Redox Biol. 2025 Oct;86:103858. doi: 10.1016/j.redox.2025.103858. Epub 2025 Sep 2.

DOI:10.1016/j.redox.2025.103858
PMID:40925124
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12454666/
Abstract

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.

摘要

铁死亡是一种以脂质过氧化过度为特征的铁依赖性细胞死亡机制，与多种人类疾病和器官病变有关。然而，目前的检测方法需要进行侵入性组织采样来评估脂质过氧化，这使得在人体中对铁死亡进行非侵入性检测极具挑战性。在本研究中，我们采用氧化挥发物组学全面表征铁死亡过程中产生的挥发性氧化脂质（VOLs）。多不饱和脂肪酸衍生的VOLs通过铁依赖性脂质过氧化（LPO）产生，并随着铁死亡的进展而释放到细胞外。这些VOLs在对乙酰氨基酚诱导的肝损伤和代谢功能障碍相关脂肪性肝炎（MASH）小鼠模型的肝脏铁死亡过程中特异性产生，并且在MASH患者的呼出气体中也可检测到。铁依赖性LPO释放的特定VOLs是体内铁死亡的潜在标志物，可能有助于对人类细胞健康进行非侵入性监测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6d4/12454666/052ee36abbc9/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6d4/12454666/7fbf7434a0bc/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6d4/12454666/31aa64ad114c/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6d4/12454666/d7b1eb7cb90a/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6d4/12454666/3e2b0e983794/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6d4/12454666/b581d4e6268b/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6d4/12454666/d24b3e82ad8e/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6d4/12454666/052ee36abbc9/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6d4/12454666/7fbf7434a0bc/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6d4/12454666/31aa64ad114c/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6d4/12454666/d7b1eb7cb90a/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6d4/12454666/3e2b0e983794/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6d4/12454666/b581d4e6268b/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6d4/12454666/d24b3e82ad8e/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6d4/12454666/052ee36abbc9/gr6.jpg

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本文引用的文献

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Recommendations for robust and reproducible research on ferroptosis.关于铁死亡的稳健且可重复研究的建议。
Nat Rev Mol Cell Biol. 2025 Apr 9. doi: 10.1038/s41580-025-00843-2.
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Liver biopsy evaluation in MASH drug development: Think thrice, act wise.在 MASH 药物开发中进行肝活检评估：三思而后行，明智行事。
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Lipid-derived electrophiles inhibit the function of membrane channels during ferroptosis.脂质衍生的亲电物在铁死亡期间抑制膜通道的功能。
Proc Natl Acad Sci U S A. 2024 May 21;121(21):e2317616121. doi: 10.1073/pnas.2317616121. Epub 2024 May 14.
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Emerging role of ferroptosis in metabolic dysfunction-associated steatotic liver disease: revisiting hepatic lipid peroxidation.铁死亡在代谢相关脂肪性肝病中的新作用：重新审视肝脂质过氧化。
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7-Dehydrocholesterol is an endogenous suppressor of ferroptosis.7-脱氢胆固醇是一种内源性的铁死亡抑制剂。
Nature. 2024 Feb;626(7998):401-410. doi: 10.1038/s41586-023-06878-9. Epub 2024 Jan 31.
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Lipid Peroxidation Drives Liquid-Liquid Phase Separation and Disrupts Raft Protein Partitioning in Biological Membranes.脂质过氧化作用驱动生物膜中的液-液相分离并破坏筏蛋白的分区。
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