2. Academic Validation
  3. Iron-Rich Particles Drive Pulmonary Toxicity of Coal Combustion-Derived Fine Particles via Transferrin Receptor-Mediated Ferroptosis

Iron-Rich Particles Drive Pulmonary Toxicity of Coal Combustion-Derived Fine Particles via Transferrin Receptor-Mediated Ferroptosis

  • Environ Sci Technol. 2026 Mar 17;60(10):7716-7732. doi: 10.1021/acs.est.5c14929.
Xiaojing Yang 1,  Yuxiang Cao 2,  Miao Xu 1,  Zuoshun Niu 1,  Mengyuan Wang 1,  Yingwen Wang 2,  Meiyao Meng 2,  Xuanhe Zhao 1,  Zhiqiang Shi 1,  Longliang Wang 1,  Xinran Ma 2,  Yi Yang 1 3 4
Affiliations

Affiliations

  • 1 Key Laboratory of Geographic Information Science of the Ministry of Education, School of Geographic Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China.
  • 2 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
  • 3 State Key Laboratory of Estuarine and Coastal Research; Yangtze Delta Estuarine Wetland Ecosystem Observation and Research Station, Ministry of Education & Shanghai, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China.
  • 4 Shanghai Key Lab for Urban Ecological Processes and Eco-Restoration, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China.
PMID: 41766572 DOI: 10.1021/acs.est.5c14929
Abstract

Coal-derived fine particles (FPs, <1 μm) are highly reactive and compositionally heterogeneous, yet their toxicity mechanisms remain poorly understood. Using single-particle ICP-TOF-MS, we profiled metal(loid)s in FPs from ten representative coal-fired power Plants across China. Quantification showed that 57 ± 9% of FPs were multimetal(loid) (mmFPs), 84 ± 9% of which were Al/Si/Fe-rich and carried most toxic metals. Toxicology assays identified that Fe-rich FPs and associated toxic metals (Cr, Mn, and Pb) could be important contributors to cellular injury, accompanied by oxidative stress and in vitro transcriptomic enrichment of Ferroptosis, inflammation, and small-cell lung cancer-related signaling pathways. As an easily separable Fe-rich FP fraction, magnetic FPs comprised only 15.8% of the mass yet contributed 74.2% of oxidative stress and 88.5% of the cytotoxicity. In vitro and in vivo experiments revealed their Transferrin Receptor (TFRC)-mediated uptake induced Ferroptosis and pulmonary injury, which could be attenuated by a TFRC inhibitor. These results suggest Fe-rich FPs (together with associated toxic metals) as the significant contributor of coal-combustion FP toxicity and provide the mechanistic evidence pinpointing Fe-rich particles as key determinants.

Keywords

TFRC; coal combustion-derived FPs; ferroptosis; pulmonary toxicity; spICP-TOF-MS.

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