2. Academic Validation
  3. Polystyrene nanoplastics carrying copper ion induce FDX1-mediated cuproptosis

Polystyrene nanoplastics carrying copper ion induce FDX1-mediated cuproptosis

  • Ecotoxicol Environ Saf. 2025 Aug 23:303:118923. doi: 10.1016/j.ecoenv.2025.118923.
Huiqi Li 1,  Qizhuan Lin 1,  Huanpeng Liu 1,  Zheyan Chen 2,  Xueliang Zhang 3,  Liyuan Jin 3,  Renyi Peng 4,  Huanzhi Jin 5
Affiliations

Affiliations

  • 1 Institute of Life Sciences & Biomedicine Collaborative Innovation Center of Zhejiang province, College of Life and Environmental Science, Wenzhou University, Wenzhou 325035, China.
  • 2 Department of Plastic Surgery, The Wenzhou Third Clinical Institute Affiliated To Wenzhou Medical University/Wenzhou People's Hospital, Wenzhou, China.
  • 3 Department of General Practice, The Wenzhou Third Clinical Institute Affiliated To Wenzhou Medical University/Wenzhou People's Hospital, Wenzhou, China.
  • 4 Institute of Life Sciences & Biomedicine Collaborative Innovation Center of Zhejiang province, College of Life and Environmental Science, Wenzhou University, Wenzhou 325035, China. Electronic address: 20170032@wzu.edu.cn.
  • 5 Department of General Practice, The Wenzhou Third Clinical Institute Affiliated To Wenzhou Medical University/Wenzhou People's Hospital, Wenzhou, China. Electronic address: jinhuanzhi@sina.cn.
PMID: 40850113 DOI: 10.1016/j.ecoenv.2025.118923
Abstract

Polystyrene nanoplastics (PS-NPs) and copper ions (Cu²⁺) are common environmental pollutants, yet their combined toxicological effects remain poorly understood. This study demonstrates that PS-NPs act as carriers of Cu²⁺, facilitating intracellular accumulation and inducing Cuproptosis, a recently identified form of regulated cell death. Using zebrafish larvae and Hep G2 cells, we showed that co-exposure to PS-NPs and Cu²⁺ disrupted copper homeostasis, promoted DLAT oligomerization, impaired mitochondrial structure and function, and activated the Cuproptosis pathway. Molecular docking revealed stable binding of PS-NPs and Cu²⁺ to the key regulator FDX1, further aggravating Cuproptosis. FDX1 overexpression experiments confirmed its pivotal role, as enhanced expression significantly increased DLAT aggregation and cell death. This study is the first to reveal the molecular mechanism by which PS-NPs mediate FDX1-dependent Cuproptosis via a "Trojan horse" effect. These findings provide novel insights into the mechanisms of nanoplastics-heavy metal co-exposure and offer a potential molecular target for mitigating environmental toxicity.

Keywords

Cu(2+); Cuproptosis; FDX1; Hep G2; Zebrafish larvae; polystyrene nanoplastics.

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