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  3. Disability in mitochondrial aerobic metabolism and Mg2+ transport: linking biomarkers and mechanisms of ischemic heart disease to diesel particulate matter exposure

Disability in mitochondrial aerobic metabolism and Mg2+ transport: linking biomarkers and mechanisms of ischemic heart disease to diesel particulate matter exposure

  • BMC Med. 2025 Jul 1;23(1):379. doi: 10.1186/s12916-025-04212-w.
Ze Zhang # 1,  Gan Miao # 1,  Juan Ma 2,  Ziyuan Li 1,  Chuer Zheng 1,  Jian Ding 1,  Hao Yin 1,  Xiangcheng Cui 3,  Shoujie Dai 3,  Rifat Zubair Ahmed 4,  Yong Niu 5,  Shanfa Yu 6,  Xiaoting Jin 7,  Yuxin Zheng 8
Affiliations

Affiliations

  • 1 Department of Occupational Health and Environmental Health, School of Public Health, Qingdao University, Qingdao, China.
  • 2 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
  • 3 Pingdu Municipal Centers for Diseases Control and Prevention, Qingdao, China.
  • 4 Department of Genetics, University of Karachi, Karachi, Pakistan.
  • 5 Key Laboratory of Chemical Safety and Health, Chinese Center for Disease Control and Prevention, National Institute for Occupational Health and Poison Control, Beijing, China.
  • 6 Department of Public Health, Henan Medical College, Zhengzhou, China.
  • 7 Department of Occupational Health and Environmental Health, School of Public Health, Qingdao University, Qingdao, China. xtjin@qdu.edu.cn.
  • 8 Department of Occupational Health and Environmental Health, School of Public Health, Qingdao University, Qingdao, China. yxzheng@qdu.edu.cn.
  • # Contributed equally.
PMID: 40598160 DOI: 10.1186/s12916-025-04212-w
Abstract

Background: Ischemic heart disease (IHD) is a major cardiovascular health concern. In addition to metabolic and behavioral risks, diesel particulate matter (DPM), with a widely exposed population, is an important external environmental risk factor for IHD. However, the effect biomarkers used to diagnose DPM-caused IHD and underlying mechanisms remain unknown. We investigated the biomarkers and underlying mechanisms of DPM in relation to myocardial hypoxia injury.

Methods: This study applied a unique population of diesel engine testers with stable DPM exposure. Electrocardiogram examination, echocardiogram examination, serum levels of myocardial Enzymes, and 6-min walking test were used for the myocardial risks assessment. A mouse model exposed to occupational environmental DPM dose and in vitro models of DPM-induced myocardial hypoxia injury were used for assessment of mitochondrial aerobic metabolism via the oxygraph-2k system, western blotting, and kits. Ion fluorescence probes, ion supplements, and mitochondrial RNA splicing protein 2 (Mrs2) overexpression transfection were used in further investigations and verifications of the mechanism of mitochondrial Mg2+ deficiency.

Results: We identified compromised myocardial mitochondrial aerobic metabolism as a precursor biomarker for the cardiac risk of myocardial hypertrophy and hypoxia injury in DPM exposure. DPM induce mitochondrial Mg2+ deficiency of cardiomyocytes, which in turn disrupt the mitochondrial aerobic metabolism processes, including the tricarboxylic acid cycle, Oxidative Phosphorylation, and ATP synthesis. Mg2+ deficiency is mediated by the disruption of Mg2+ transport proteins, such as DPM-enhanced hyperubiquitination and degradation of Mrs2, a protein responsible for mitochondrial Mg2+ uptake.

Conclusions: Our findings show that compromised mitochondrial aerobic metabolism, associated with Mg2+ deficiency, serves as a critical biomarker for DPM-induced IHD and represents a promising investigative avenue for intervention.

Keywords

Diesel particulate matter; Ischemic heart disease; Mg2+ transport; Mitochondrial aerobic metabolism.

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