Membrane Proteins: Targets That Should Not Be Overlooked for Assessing Human and Ecological Health Effects of...

The potential toxicities of chemicals to humans and wildlife remain largely unknown. In vitro bioassays have increasingly been applied for the toxicity testing of chemicals. However, most of these assays target nuclear receptors, with a very limited number targeting membrane proteins (e.g., receptors, transporters, and ion channels). Membrane proteins are an important protein group. They outnumber nuclear receptors by 2 orders of magnitude, play important roles in many physiological processes, and are highly conserved across species. Chemicals targeting membrane proteins might trigger more severe adverse effects. Despite their significance, the adverse effects of chemicals on membrane proteins have largely been overlooked. To promote the assessment of human and ecological health effects of chemicals, this perspective summarizes the categories and functions of important membrane proteins, adverse effects of chemicals on humans and wildlife by targeting membrane proteins, and the available membrane protein-targeting in vitro bioassays in toxicity testing. Furthermore, we discuss keys to develop bioassays and computational tools for investigating the toxicity of chemicals against membrane proteins. Greater attention should be paid to membrane proteins when assessing human and ecological health effects of chemicals in future research.