John J. Lemasters, M.D., Ph.D.

John Lemasters, Ph.D.

Department: Drug Discovery & Biomedical Sciences
Programs: Cell Injury, Inflammation, Fibrosis
Imaging Core



Research Interests:

Dr. Lemasters earned his MD and PhD from the Johns Hopkins University School of Medicine in 1975. Over the course of his career as a faculty member at the University of Texas Health Science Center Southwestern Medical School, University of North Carolina at Chapel Hill, and Medical University of South Carolina (MUSC), he has published over 350 papers in peer-reviewed journals, more than 100 book chapters, received 6 patents, and edited 4 books. Productive, long-term collaborations with junior and senior colleagues contributed importantly to this success.

Dr. Lemasters has a long-standing interest in the role of mitochondrial metabolism in hepatopathobiology, especially in relation to ischemia-reperfusion (IR) injury, ethanol/drug-induced hepatic injury, liver preservation for transplantation, cancer, and mitochondrial autophagy (mitophagy). His in vitro and in vivo studies of living cells and tissues have shown that mitochondrial calcium uptake, iron translocation from lysosomes to mitochondria and oxidative stress promote the mitochondrial permeability transition (MPT). The MPT initially induces lysosomal degradation of mitochondria by autophagy, a selective process called mitophagy. However, after ischemia/reperfusion, oxidative stress, liver storage and transplantation, acetaminophen hepatotoxicity and other stresses to the liver, excess MPT onset induces both necrotic cell death from ATP depletion and apoptosis due to cytochrome c release after mitochondrial swelling. Dr. Lemasters has also shown similar events occurring in cardiac myocytes subjected to ischemia/reperfusion.

Despite a detailed understanding of their metabolism, mitochondria often behave anomalously. In particular, global suppression of mitochondrial metabolism and metabolite exchange occurs in apoptosis, ischemia/hypoxia, alcoholic liver disease and aerobic glycolysis in cancer cells (Warburg effect). Dr. Lemasters’ lab is examining and supporting the novel hypotheses that closure of voltage-dependent anion channels (VDAC) in the mitochondrial outer membrane accounts for global mitochondrial suppression consistent with a role for VDAC as a dynamic regulator, or governator, of mitochondrial function both in health and disease. Moreover, a switch from electrogenic to non-electrogenic mitochondrial ATP/ADP exchange in proliferating cancer cells leads to lower cytosolic ATP/ADP ratios and stimulation of aerobic glycolysis.


PubMed Collection