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One or more keywords matched the following properties of Lemasters, John
overview I have a long-standing interest in hepatic ischemia-reperfusion (IR) injury, especially as it relates to organ preservation for transplantation. I and my colleagues were the first to show a prominent role for nonparenchymal cells in IR injury to cold-stored livers. Specifically, we showed that reperfusion after cold ischemic storage leads to killing of sinusoidal endothelial cells and activation of Kupffer cells. We were also pioneers in showing that onset of the mitochondrial permeability transition (MPT) then developed in hepatic parenchymal cells, leading to hepatic apoptosis, necrosis and graft failure, and we developed a variety of stratagems to ameliorate these injuries that are beginning to find clinical application. Overall, my laboratory has published over 350 papers in peer-reviewed journals plus more than 100 book chapters. Productive, long-term collaborations with both junior and senior colleagues contributed importantly to this success. My research interests continue to relate to mitochondrial and cellular bioenergetics, including studies of oxidative phosphorylation in isolated mitochondria, mitochondrial dysfunction in toxic, and hypoxic and reperfusion injury to liver and heart cells, and graft failure from preservation injury to livers stored for transplantation surgery. Our 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 MPT. The MPT initially induces lysosomal degradation of mitochondria by autophagy, a selective process called mitophagy. However, excess MPT induction induces both necrotic cell death from ATP depletion and apoptosis due to cytochrome c release after mitochondrial swelling. For these projects, my laboratory extensively applies new techniques of quantitative laser scanning confocal and intravital multiphoton microscopy for physiological analysis of single cells and living organs. The lab also extensively employs Seahorse technology to measure respiration and glycolytic flux in cultured cells. Current projects are examining how iron mobilization from lysosomes to cytosol and then to mitochondria during cold ischemic liver storage sensitizes hepatocytes and nonparenchymal cells to adverse events after reperfusion, leading ultimately to injury and failure of liver grafts. 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). My lab is also examining and supporting the novel hypothesis 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 global mitochondrial function both in health and disease. In cancer cells, we showed that free tubulin causes closure of VDAC.
One or more keywords matched the following items that are connected to Lemasters, John
Item TypeName
Academic Article The mitochondrial permeability transition is required for tumor necrosis factor alpha-mediated apoptosis and cytochrome c release.
Academic Article NF-kappaB stimulates inducible nitric oxide synthase to protect mouse hepatocytes from TNF-alpha- and Fas-mediated apoptosis.
Academic Article Bid activates multiple mitochondrial apoptotic mechanisms in primary hepatocytes after death receptor engagement.
Academic Article Roles of mitophagy and the mitochondrial permeability transition in remodeling of cultured rat hepatocytes.
Academic Article Cyclophilin D deficiency protects against acetaminophen-induced oxidant stress and liver injury.
Academic Article Ethanol suppresses ureagenesis in rat hepatocytes: role of acetaldehyde.
Academic Article Gliotoxin-mediated apoptosis of activated human hepatic stellate cells.
Academic Article Lateral diffusion of ubiquinone during electron transfer in phospholipid- and ubiquinone-enriched mitochondrial membranes.
Academic Article The energized state of rat liver mitochondria. ATP equivalence, uncoupler sensitivity, and decay kinetics.
Academic Article Relationships between bilayer lipid, motional freedom of oxidoreductase components, and electron transfer in the mitochondrial inner membrane.
Academic Article Apoptosis and necrosis in the liver: a tale of two deaths?
Academic Article Nuclear translocation of endonuclease G and apoptosis-inducing factor during acetaminophen-induced liver cell injury.
Academic Article NIM811 prevents mitochondrial dysfunction, attenuates liver injury, and stimulates liver regeneration after massive hepatectomy.
Academic Article Liposome-mitochondrial inner membrane fusion. Lateral diffusion of integral electron transfer components.
Academic Article Thermodynamic limits to the ATP/site stoichiometries of oxidative phosphorylation by rat liver mitochondria.
Concept Cytochrome P-450 CYP2E1
Concept Cytochrome P-450 Enzyme System
Concept Cytochromes c1
Concept Cytochromes
Concept Succinate Cytochrome c Oxidoreductase
Concept Cytochrome c Group
Concept Cytochromes c
Academic Article Acute ethanol causes hepatic mitochondrial depolarization in mice: role of ethanol metabolism.
Academic Article Effect of the CRAC Peptide, VLNYYVW, on mPTP Opening in Rat Brain and Liver Mitochondria.
Academic Article 2',3'-Cyclic nucleotide 3'-phosphodiesterase as a messenger of protection of the mitochondrial function during melatonin treatment in aging.
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  • Cytochromes