Downregulation of TAZ elicits a mitochondrial redox imbalance and ferroptosis in lung epithelial cells exposed to diesel exhaust particles

doi:10.1016/j.ecoenv.2023.115555

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Title:	Downregulation of TAZ elicits a mitochondrial redox imbalance and ferroptosis in lung epithelial cells exposed to diesel exhaust particles
Authors:	Lee, Kang-Yun Yang, Ching-Chieh Shueng, Pei-Wei Wu, Sheng-Min Chen, Chih-Hsuan Chao, Yi-Chun Chang, Yu-Chu Han, Chia-Li Chuang, Hsiao-Chi Lee, Chi-Ching Lin, Cheng-Wei
Contributors:	Taipei Med Univ, Coll Med, Sch Med, Div Pulm Med,Dept Internal Med Taipei Med Univ, Shuang Ho Hosp, Dept Internal Med, Div Pulm Med Chi Mei Med Ctr, Div Hematol Oncol Chia Nan Univ Pharm & Sci, Dept Pharm Far Eastern Mem Hosp, Div Radiat Oncol Natl Yang Ming Chiao Tung Univ, Fac Med, Sch Med Taipei Med Univ, Coll Med, Sch Med, Dept Biochem & Mol Cell Biol Taipei Med Univ, Coll Pharm, Master Program Clin Genom & Prote Taipei Med Univ, Coll Med, Sch Resp Therapy Istanbul Sabahattin Zaim Univ, Fac Engn & Nat Sci, Dept Food Engn Taipei Med Univ, Wan Fang Hosp, Cell Physiol & Mol Image Res Ctr Kaohsiung Med Univ, Drug Dev & Value Creat Res Ctr
Keywords:	Ferroptosis COPD Particular matter Mitochondrial redox Hippo
Date:	2023
Issue Date:	2024-12-25 11:04:38 (UTC+8)
Publisher:	ACADEMIC PRESS INC ELSEVIER SCIENCE
Abstract:	Mitochondrial dysfunction was reported to be involved in the development of lung diseases including chronic obstructive pulmonary disease (COPD). However, molecular regulation underlying metabolic disorders in the airway epithelia exposed to air pollution remains unclear. In the present study, lung bronchial epithelial BEAS-2B and alveolar epithelial A549 cells were treated with diesel exhaust particles (DEPs), the primary representative of ambient particle matter. This treatment elicited cell death accompanied by induction of lipid reactive oxygen species (ROS) production and ferroptosis. Lipidomics analyses revealed that DEPs increased glycerophospholipid contents. Accordingly, DEPs upregulated expression of the electron transport chain (ETC) complex and induced mitochondrial ROS production. Mechanistically, DEP exposure downregulated the Hippo transducer transcrip-tional co-activator with PDZ-binding motif (TAZ), which was further identified to be crucial for the ferroptosis-associated antioxidant system, including glutathione peroxidase 4 (GPX4), the glutamate-cysteine ligase catalytic subunit (GCLC), and glutathione-disulfide reductase (GSR). Moreover, immunohistochemistry confirmed downregulation of GPX4 and upregulation of lipid peroxidation in the bronchial epithelium of COPD patients and Sprague-Dawley rats exposed to air pollution. Finally, proteomics analyses confirmed alterations of ETC-related proteins in bronchoalveolar lavage from COPD patients compared to healthy subjects. Together, our study discovered that involvement of mitochondrial redox dysregulation plays a vital role in pulmonary epithelial cell destruction after exposure to air pollution.
Relation:	Ecotoxicology and Environmental Safety, v.266, Article 115555
Appears in Collections:	[Offices] 456

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