The major function of mitochondria in cellular homeostasis has been the generation of ATP through oxidative phosphorylation. However, Dr. Chandel’s team has previously demonstrated that mitochondria can serve as signaling organelles by releasing low levels of reactive oxygen species (ROS) that are essential for hypoxic responses, antigen activation of T cells, cellular differentiation, and proliferation of cancer cells. Their recent findings indicate that mitochondria also release TCA cycle metabolites that are necessary for chromatin and DNA modifications to control Treg cell suppressive function and stem cell function. Dr. Chandel will present his group’s current findings on how mitochondria affect cellular function beyond ATP production through ROS, and TCA cycle metabolites control physiology and disease relevant to immunity, cancer, and neurodegeneration.
Dr. Navdeep S. Chandel is the David W. Cugell Professor of Medicine and Biochemistry & Molecular Genetics at Northwestern University. He received his BA in Mathematics and PhD in Cell Physiology at the University of Chicago. For decades, the mitochondria have been primarily viewed as biosynthetic and bioenergetic organelles generating metabolites for the production of macromolecules and ATP, respectively. Dr. Chandel’s work has elucidated that mitochondria have a third distinct role whereby they participate in cellular signaling processes through the release of reactive oxygen species (ROS) and TCA cycle metabolites independent of ATP and macromolecule production. His work has implicated the necessity of mitochondrial ROS for multiple biological processes including cancer cell proliferation, hypoxic activation of HIFs, cellular differentiation, and immune cell function. Previously, the dogma in the field had been that mitochondrial ROS are only produced in pathological settings to cause both cellular and DNA damage. However, Dr. Chandel’s work demonstrates that mitochondrial ROS are utilized as messengers to maintain normal biological and physiological functions. His studies suggest that the current widespread use of antioxidants is likely to be detrimental rather than beneficial for alleviating a myriad of diseases, as this could interfere with normal physiological processes. Recently, his work has shown how mitochondrial metabolites influence histone modifications and DNA methylation to control stem and immune cell function. Dr. Chandel has published over 220 articles and a book entitled “Navigating Metabolism.” He received the National Cancer Institute Outstanding Investigator Award in 2016.