Identification and characterization of environmental chemicals that affect mitochondrial function
Menghang Xia National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA
Mitochondria, a power house of the cells, play a critical role in cellular physiology. Mitochondria generate chemical energy in the form of adenosine triphosphate (ATP) through the electron transport chain (ETC), which creates an electrochemical gradient through a series of redox reactions. This electrochemical gradient drives the synthesis of ATP and generates the mitochondrial membrane potential (MMP), which is a key parameter for evaluating mitochondrial function. As the part of Tox21 program, a cell-based MMP assay has been used to screen the Tox21 chemicals in a qHTS platform. From the primary screening, a group of chemical compounds that decreased the MMP have been identified. These identified compounds have been further tested in several tired secondary assays, including mitochondrial related signaling pathways (ROS, p53 and Nrf2/ARE) and mitochondrial functions (oxygen consumption, complex activity and Parkin translocation). The data generated from this study will be useful for prioritizing chemicals for further in-depth mechanism-based toxicity testing.
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