PM2.5 induces mitochondrial damage-triggered ferroptosis in renal tubular cells leading to renal injury

  • Chem Biol Interact. 2026 Jul 25:435:112163. doi: 10.1016/j.cbi.2026.112163.
Weilin Chen  1 ,  Mengqian Liu  2 ,  Jingjing Quan  2 ,  Yueyi Zhou  2 ,  Zishun Zhan  2 ,  Ji Zhou  3 ,  Bin Yi  4 ,  Zhijun Huang  5
Affiliations
  • 1. Department of Nephrology, The Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha, Hunan, 410013, China; Department of Nephrology, The Second Affiliated Hospital of University of South China, 35 Jiefang Road, Hengyang, Hunan, 421000, China.
  • 2. Department of Nephrology, The Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha, Hunan, 410013, China.
  • 3. Typhoon Institute/CMA, Shanghai Key Laboratory of Meteorology and Health, Shanghai, 200030, China.
  • 4. Department of Nephrology, The Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha, Hunan, 410013, China. Electronic address: [email protected].
  • 5. Department of Nephrology, The Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha, Hunan, 410013, China; Furong Laboratory, Changsha, Hunan, 410013, China; Center for Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China. Electronic address: [email protected].
PMID: 42173391 DOI: 10.1016/j.cbi.2026.112163
Abstract

Renal injury associated with fine particulate matter (PM2.5) exposure has become increasingly prominent. Currently, research on the mechanisms of PM2.5-induced renal cell dysfunction is limited. To investigate PM2.5-induced kidney damage, we constructed a 12-week PM2.5 exposure model in C57BL/6 mice. We then collected urine, blood, and kidney tissue samples to assess pathological and functional changes. To further elucidate the molecular mechanisms of PM2.5-induced renal injury, we concurrently established an in vitro model using Bumpt cells for PM2.5 exposure. In vivo and in vitro results demonstrated that PM2.5 exposure induced significant damage to proximal tubular epithelial cells and their mitochondria, which was characterized by marked decreases in mitochondrial membrane potential and membrane fluidity, abnormal mitochondrial morphological changes including shortened branch length, enhanced fission and inhibited fusion, as well as increased production of mitochondrial-derived Reactive Oxygen Species (ROS). These findings suggested that mitochondrial structural and functional disorders might serve as a key mechanism underlying PM2.5-mediated renal injury. Based on mRNA Sequencing results from kidney tissues, the roles of mitochondrial dysfunction and Ferroptosis were validated in PM2.5-induced proximal tubular epithelial cell injury. Our results also confirmed that PM2.5 exposure elevated ferroptosis-related biomarkers. Importantly, at lower concentrations of PM2.5 exposure, mitochondrial lipid peroxidation exhibited higher sensitivity to PM2.5 stimulation compared to intracellular lipid peroxidation. Furthermore, MitoQ had a better rescue effect than Fer-1 in ameliorating the above changes triggered by PM2.5 exposure. These results indicate that PM2.5 exposure-induced renal injury is dependent on ROS derived from mitochondrial damage, which exacerbates lipid peroxidation and Ferroptosis.

Keywords
Ferroptosis; Fine particulate matter; Mitochondria; Renal injury.
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