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线粒体功能障碍作为环境损伤的标志。

Mitochondrial Dysfunction as a Hallmark of Environmental Injury.

机构信息

Environmental Toxicity, Therapeutic Targets, Cellular Signaling and Biomarkers, T3S, INSERM UMR-S 1124, F-75006 Paris, France.

Faculty of Sciences, Université de Paris, F-75006 Paris, France.

出版信息

Cells. 2021 Dec 30;11(1):110. doi: 10.3390/cells11010110.

Abstract

Environmental factors including diet, sedentary lifestyle and exposure to pollutants largely influence human health throughout life. Cellular and molecular events triggered by an exposure to environmental pollutants are extremely variable and depend on the age, the chronicity and the doses of exposure. Only a fraction of all relevant mechanisms involved in the onset and progression of pathologies in response to toxicants has probably been identified. Mitochondria are central hubs of metabolic and cell signaling responsible for a large variety of biochemical processes, including oxidative stress, metabolite production, energy transduction, hormone synthesis, and apoptosis. Growing evidence highlights mitochondrial dysfunction as a major hallmark of environmental insults. Here, we present mitochondria as crucial organelles for healthy metabolic homeostasis and whose dysfunction induces critical adverse effects. Then, we review the multiple mechanisms of action of pollutants causing mitochondrial toxicity in link with chronic diseases. We propose the Aryl hydrocarbon Receptor (AhR) as a model of "exposome receptor", whose activation by environmental pollutants leads to various toxic events through mitochondrial dysfunction. Finally, we provide some remarks related to mitotoxicity and risk assessment.

摘要

环境因素,包括饮食、 sedentary 生活方式和暴露于污染物,在人的一生当中在很大程度上影响着人类健康。暴露于环境污染物所引发的细胞和分子事件变化极大,取决于暴露的年龄、慢性程度和剂量。可能只有一小部分与毒物引起的病理发生和进展相关的所有相关机制已被确定。线粒体是代谢和细胞信号的中心枢纽,负责多种生化过程,包括氧化应激、代谢物产生、能量转导、激素合成和细胞凋亡。越来越多的证据强调线粒体功能障碍是环境损伤的主要标志。在这里,我们将线粒体呈现为健康代谢稳态的关键细胞器,其功能障碍会引发严重的不良反应。然后,我们回顾了污染物引起线粒体毒性与慢性疾病之间联系的多种作用机制。我们提出芳烃受体 (AhR) 作为“暴露组受体”的模型,其通过环境污染物的激活导致通过线粒体功能障碍的各种毒性事件。最后,我们就线粒体毒性和风险评估提供了一些看法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2efb/8750015/163acda46426/cells-11-00110-g001.jpg

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