Revelations from the Nematode Caenorhabditis elegans on the Complex Interplay of Metal Toxicological Mechanisms

Figure 1

Metal detoxification systems. GSH is converted to GSSG upon exposure to ROS. GR converts GSSG back to GSH while converting NADPH to NADP+. γGCS is the rate-limiting enzyme in GSH synthesis. GSTs assist with the conjugation of GSH to the metal for excretion from the system. Additionally, GSH is known to be protective against metal-generated ROS by binding free radicals. PCs are thiol-rich peptides that can complex with metals and act as chelators. MTs can directly bind and sequester the toxicant and act as antioxidants. ATP-binding cassette (ABC) transporters contribute to heavy metal tolerance by facilitating the excretion of metals, including metals that are conjugated to GS−. HSP70s are ATP-binding proteins that convert ATP to ADP and bind to metals and other proteins, thereby inactivating them and preventing aggregation.