Exposure to arsenic in contaminated drinking water is a worldwide public health problem that affects more than 200 million people. Protein quality control constitutes an evolutionarily conserved mechanism for promoting proper folding of proteins, refolding of misfolded proteins, and removal of aggregated proteins, thereby maintaining homeostasis of the proteome (i.e., proteostasis). Accumulating lines of evidence from epidemiological and laboratory studies revealed that chronic exposure to inorganic arsenic species can elicit proteinopathies that contribute to neurodegenerative disorders, cancer, and type II diabetes. Here, we review the effects of arsenic exposure on perturbing various elements of the proteostasis network, including mitochondrial homeostasis, molecular chaperones, inflammatory response, ubiquitin-proteasome system, autophagy, as well as asymmetric segregation and axonal transport of misfolded proteins. We also discuss arsenic-induced disruptions of post-translational modifications of proteins, for example, ubiquitination, and their implications in proteostasis. Together, studies in the past few decades support that disruption of protein quality control may constitute an important mechanism underlying the arsenic-induced toxicity.

中文翻译：

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砷暴露和蛋白质质量控​​制受损。

在受污染的饮用水中接触砷是一个全球性的公共卫生问题，影响了超过2亿人。蛋白质质量控​​制构成了一种进化上保守的机制，可促进蛋白质的正确折叠，错误折叠的蛋白质的重新折叠以及聚集蛋白的去除，从而维持蛋白质组的稳态（即蛋白质稳态）。流行病学和实验室研究得出的越来越多的证据表明，长期暴露于无机砷物种会引起导致神经退行性疾病，癌症和II型糖尿病的蛋白病。在这里，我们回顾了砷暴露对摄动蛋白稳态网络各种要素的影响，包括线粒体稳态，分子伴侣，炎症反应，泛素-蛋白酶体系统，自噬，以及错误折叠的蛋白质的不对称分离和轴突运输。我们还讨论了砷诱导的蛋白质翻译后修饰（如泛素化）的破坏及其在蛋白稳定中的影响。总之，过去几十年的研究表明，破坏蛋白质质量控​​制可能是砷诱导毒性的重要机制。