What Are the Mechanisms of Proteostasis Disruption by Toxicants?
Toxicants can disrupt proteostasis through various mechanisms:
Oxidative Stress: Many toxicants generate reactive oxygen species (ROS), which can damage proteins by oxidizing amino acid residues, leading to misfolding and aggregation. Inhibition of Proteasome: Some toxicants can inhibit the proteasome, a complex responsible for degrading ubiquitinated proteins, leading to an accumulation of defective proteins. Endoplasmic Reticulum Stress: Toxicants causing ER stress can lead to an imbalance in calcium homeostasis, impacting protein folding and maturation. Direct Binding: Certain toxicants can directly bind to proteins, altering their structure and function.
