Regina D. Schnegelberger, Anna L. Lang, Gavin E. Arteel, Juliane I. Beier. Environmental toxicant-induced maladaptive mitochondrial changes: A potential unifying mechanism in fatty liver disease?[J]. Acta Pharmaceutica Sinica B, 2021, 11(12): 3756-3767

Environmental toxicant-induced maladaptive mitochondrial changes: A potential unifying mechanism in fatty liver disease?
Regina D. Schnegelbergera, Anna L. Langb, Gavin E. Arteelc,d, Juliane I. Beierc,d,e
a. Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15213, USA;
b. Department of Neurology, University of Miami Miller School of Medicine, Miami, FL 33136, USA;
c. Department of Medicine, Division of Gastroenterology, Hepatology & Nutrition, University of Pittsburgh, Pittsburgh, PA 15213, USA;
d. Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA 15213, USA;
e. Department of Environmental & Occupational Health, University of Pittsburgh, Pittsburgh, PA 15213, USA
Occupational and environmental exposures to industrial chemicals are well known to cause hepatotoxicity and liver injury. However, despite extensive evidence showing that exposure can lead to disease, current research approaches and regulatory policies fail to address the possibility that subtle changes caused by low level exposure to chemicals may also enhance preexisting conditions. In recent years, the conceptual understanding of the contribution of environmental chemicals to liver disease has progressed significantly. Mitochondria are often target of toxicity of environmental toxicants resulting in multisystem disorders involving different cells, tissues, and organs. Here, we review persistent maladaptive changes to mitochondria in response to environmental toxicant exposure as a mechanism of hepatotoxicity. With better understanding of the mechanism(s) and risk factors that mediate the initiation and progression of toxicant-induced liver disease, rational targeted therapy can be developed to better predict risk, as well as to treat or prevent this disease.
Key words:    Organochlorines    Metals    Persistent organic pollutants    TASH    Liver disease    Hepatotoxicity    Mitochondrial maladaptation    Mitohormesis   
Received: 2021-05-04     Revised: 2021-06-29
DOI: 10.1016/j.apsb.2021.09.002
Funds: This study was funded by awards from the National Institutes of Health: K01 DK096042, R03 DK107912, R21 ES031531, P30DK120531 and P20GM113226, USA.
Corresponding author: Juliane I. Beier,
Author description:
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Regina D. Schnegelberger
Anna L. Lang
Gavin E. Arteel
Juliane I. Beier

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