Arsenic Exposure and Compromised Protein Quality Control

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.