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Mitochondrial stress response in drug-induced liver injury

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Abstract

Drug-induced liver injury (DILI) caused by the ingestion of medications, herbs, chemicals or dietary supplements, is a clinically widespread health problem. The underlying mechanism of DILI is the formation of reactive metabolites, which trigger mitochondrial oxidative stress and the opening of mitochondrial permeability transition (MPT) pores through direct toxicity or immune response, leading to cell inflammation, apoptosis, and necrosis. Traditionally, mitochondria play an indispensable role in maintaining the physiological and biochemical functions of cells by producing ATP and mediating intracellular signal transduction; drugs can typically stimulate the mitochondria and, in the case of sustained stress, can eventually cause impairment of mitochondrial function and metabolic activity. Meanwhile, the mitochondrial stress response, as an adaptive protective mechanism, occurs when mitochondrial homeostasis is threatened. In this review, we summarize the relevant frontier researches of the protective effects of mitochondrial stress response in DILI as well as the potential related mechanisms, thus providing some thoughts for the clinical treatment of DILI.

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Funding

Funding for this study was provided by National Nature Science Foundation of China (Grant No. 81100281), Hubei Provincial Natural Science Foundation of China (Grant No. 2020CFB371), and Medical and Health Research Project from Yichang Science and Technology Bureau (Grant No. A15301-35).

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Authors and Affiliations

  1. Department of Microbiology and Immunology, The Institute of Infection and Inflammation, Medical College, China Three Gorges University, No. 8 DaXue Road, Yichang, 443002, Hubei, China

    Jing Zheng, Qiulin Yuan, Cao Zhou, Weifeng Huang & Xiang Yu

  2. Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), School of Pharmacy, Ministry of Education, Yantai University, Yantai, 264005, China

    Weifeng Huang

  3. The People’s Hospital of China Three Gorges University, Yichang, 443000, China

    Jing Zheng

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  1. Jing Zheng
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  2. Qiulin Yuan
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  3. Cao Zhou
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  4. Weifeng Huang
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  5. Xiang Yu
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Contributions

WH, XY, JZ, QY and CZ contributed to the writing, review, and editing of the manuscript. JZ made the figures and tables. All authors read and approved the final manuscript.

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Correspondence to Xiang Yu.

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Zheng, J., Yuan, Q., Zhou, C. et al. Mitochondrial stress response in drug-induced liver injury. Mol Biol Rep 48, 6949–6958 (2021). https://doi.org/10.1007/s11033-021-06674-6

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