Environmental toxicant-induced maladaptive mitochondrial changes: A potential unifying mechanism in fatty liver disease?
Environmental toxicant-induced maladaptive mitochondrial changes: A potential unifying mechanism in fatty liver disease?
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DOI：
10.1016/j.apsb.2021.09.002
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Beier JI
中科院分区：
文献类型：
--
作者：
Schnegelberger RD;Lang AL;Arteel GE;Beier JI
众所周知，工业化学品的职业和环境暴露会导致肝毒性和肝损伤。然而，尽管有大量证据表明接触化学品可能导致疾病，但目前的研究方法和监管政策未能解决低水平接触化学品引起的细微变化也可能加剧原有疾病的可能性。近年来，对环境化学物质对肝脏疾病的贡献的概念理解取得了显着进展。线粒体是环境毒物毒性作用的靶点，常导致多系统疾病，涉及不同的细胞、组织和器官。在这里，我们回顾了持续适应不良的变化，线粒体在环境毒物暴露作为肝毒性的机制。随着对介导毒物诱导的肝病的发生和进展的机制和风险因素的更好理解，可以开发合理的靶向治疗以更好地预测风险，以及治疗或预防这种疾病。潜在的线粒体靶点包括电子传递链、线粒体膜电位（Δ Km）和通过线粒体相关膜（MAMs）的器官间通讯。这些靶点中的任何一个或几个的功能障碍可能会使损伤永久化。
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. Potential mitochondrial targets include the electron transport chain, mitochondrial membrane potential (ΔΨm), and organ-to-organ communication, via mitochondrial-associated membranes (MAMs). Dysfunction of any or several of these targets may perpetuate injury.
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