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Lemasters, John
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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 Mitochondrial oxygen radical formation during reductive and oxidative stress to intact hepatocytes.
Academic Article Role of free radicals in primary nonfunction of marginal fatty grafts from rats treated acutely with ethanol.
Academic Article Mitochondrial permeability transition in pH-dependent reperfusion injury to rat hepatocytes.
Academic Article Role of the mitochondrial permeability transition in salicylate toxicity to cultured rat hepatocytes: implications for the pathogenesis of Reye's syndrome.
Academic Article The mitochondrial permeability transition in cell death: a common mechanism in necrosis, apoptosis and autophagy.
Academic Article Confocal microscopy of the mitochondrial permeability transition in necrotic cell killing, apoptosis and autophagy.
Academic Article Mitochondrial dysfunction and cytoskeletal disruption during chemical hypoxia to cultured rat hepatic sinusoidal endothelial cells: the pH paradox and cytoprotection by glucose, acidotic pH, and glycine.
Academic Article Mitochondrial Ca2+ transients in cardiac myocytes during the excitation-contraction cycle: effects of pacing and hormonal stimulation.
Academic Article The mitochondrial permeability transition: from biochemical curiosity to pathophysiological mechanism.
Academic Article The mitochondrial permeability transition is required for tumor necrosis factor alpha-mediated apoptosis and cytochrome c release.
Academic Article Molecular cloning and characterization of a human mitochondrial ceramidase.
Academic Article Mitochondrial calcium transients in adult rabbit cardiac myocytes: inhibition by ruthenium red and artifacts caused by lysosomal loading of Ca(2+)-indicating fluorophores.
Academic Article Confocal microscopy of the mitochondrial permeability transition in necrotic and apoptotic cell death.
Academic Article NF-kappaB stimulates inducible nitric oxide synthase to protect mouse hepatocytes from TNF-alpha- and Fas-mediated apoptosis.
Academic Article V. Necrapoptosis and the mitochondrial permeability transition: shared pathways to necrosis and apoptosis.
Academic Article The mitochondrial permeability transition mediates both necrotic and apoptotic death of hepatocytes exposed to Br-A23187.
Academic Article Contribution of increased mitochondrial free Ca2+ to the mitochondrial permeability transition induced by tert-butylhydroperoxide in rat hepatocytes.
Academic Article Negative contrast imaging of mitochondria by confocal microscopy.
Academic Article Mitochondrial permeability transition in the switch from necrotic to apoptotic cell death in ischemic rat hepatocytes.
Academic Article Heat shock suppresses the permeability transition in rat liver mitochondria.
Academic Article Salicylate enhances necrosis and apoptosis mediated by the mitochondrial permeability transition.
Academic Article Mitochondrial permeability transition: a common pathway to necrosis and apoptosis.
Academic Article Bid activates multiple mitochondrial apoptotic mechanisms in primary hepatocytes after death receptor engagement.
Academic Article Discrimination of depolarized from polarized mitochondria by confocal fluorescence resonance energy transfer.
Academic Article Differential requirement for c-Jun NH2-terminal kinase in TNFalpha- and Fas-mediated apoptosis in hepatocytes.
Academic Article Role of mitochondrial permeability transition pores in mitochondrial autophagy.
Academic Article Mitochondrial dysfunction in the pathogenesis of necrotic and apoptotic cell death.
Academic Article The mitochondrial permeability transition and the calcium, oxygen and pH paradoxes: one paradox after another.
Academic Article Isolated mouse liver mitochondria are devoid of glucokinase.
Academic Article Tracker dyes to probe mitochondrial autophagy (mitophagy) in rat hepatocytes.
Academic Article Basal reactive oxygen species determine the susceptibility to apoptosis in cirrhotic hepatocytes.
Academic Article Apoptosis and the laws of thermodynamics.
Academic Article Increased oxidative stress is associated with balanced increases in hepatocyte apoptosis and proliferation in glycerol-3-phosphate acyltransferase-1 deficient mice.
Academic Article Role of apoptosis in acetaminophen hepatotoxicity.
Academic Article Mitochondrial permeability transition in liver ischemia and reperfusion: role of c-Jun N-terminal kinase 2.
Academic Article C-Jun N-terminal kinase 2 promotes graft injury via the mitochondrial permeability transition after mouse liver transplantation.
Academic Article Activation of the oxygen-sensing signal cascade prevents mitochondrial injury after mouse liver ischemia-reperfusion.
Academic Article Translocation of iron from lysosomes into mitochondria is a key event during oxidative stress-induced hepatocellular injury.
Academic Article Ethanol exposure decreases mitochondrial outer membrane permeability in cultured rat hepatocytes.
Academic Article Mechanisms of hepatotoxicity.
Academic Article Regulated and unregulated mitochondrial permeability transition pores: a new paradigm of pore structure and function?
Academic Article Roles of mitophagy and the mitochondrial permeability transition in remodeling of cultured rat hepatocytes.
Academic Article Closure of VDAC causes oxidative stress and accelerates the Ca(2+)-induced mitochondrial permeability transition in rat liver mitochondria.
Academic Article Mechanisms of pathogenesis in drug hepatotoxicity putting the stress on mitochondria.
Academic Article Cyclophilin D deficiency protects against acetaminophen-induced oxidant stress and liver injury.
Academic Article [The role of the voltage-dependent anion channels in the outer membrane of mitochondria in the regulation of cellular metabolism].
Academic Article Mitochondrial degradation by autophagy (mitophagy) in GFP-LC3 transgenic hepatocytes during nutrient deprivation.
Academic Article Mitophagy selectively degrades individual damaged mitochondria after photoirradiation.
Academic Article Free tubulin modulates mitochondrial membrane potential in cancer cells.
Academic Article Sphingosine kinase-2 inhibition improves mitochondrial function and survival after hepatic ischemia-reperfusion.
Academic Article Continuous measurement of adenosine triphosphate with firefly luciferase luminescence.
Academic Article Regulation of mitochondrial function by voltage dependent anion channels in ethanol metabolism and the Warburg effect.
Academic Article Ethanol suppresses ureagenesis in rat hepatocytes: role of acetaldehyde.
Academic Article Mitochondrial permeability transition in rat hepatocytes after anoxia/reoxygenation: role of Ca2+-dependent mitochondrial formation of reactive oxygen species.
Academic Article Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy.
Academic Article Mitoferrin-2-dependent mitochondrial iron uptake sensitizes human head and neck squamous carcinoma cells to photodynamic therapy.
Academic Article Role of mitochondrial inner membrane permeabilization in necrotic cell death, apoptosis, and autophagy.
Academic Article Translocation of iron from lysosomes to mitochondria during ischemia predisposes to injury after reperfusion in rat hepatocytes.
Academic Article Isolated mitochondria infusion mitigates ischemia-reperfusion injury of the liver in rats: mitotracker probes and mitochondrial membrane potential.
Academic Article Gliotoxin-mediated apoptosis of activated human hepatic stellate cells.
Academic Article Green tea polyphenols stimulate mitochondrial biogenesis and improve renal function after chronic cyclosporin a treatment in rats.
Academic Article Rhodamine 123 as a probe of transmembrane potential in isolated rat-liver mitochondria: spectral and metabolic properties.
Academic Article An ATP/2e-stoichiometry of 1 1/2 is thermodynamically possible for site 3 of oxidative phosphorylation.
Academic Article Blebbing, free Ca2+ and mitochondrial membrane potential preceding cell death in hepatocytes.
Academic Article Possible role of the mitochondrial outer membrane as an oncotic regulator of mitochondrial volume.
Academic Article Phosphate dependence and atractyloside inhibition of mitochondrial oxidative phosphorylation. The ADP-ATP carrier is rate-limiting.
Academic Article Adenosine triphosphate: continuous measurement in mitochondrial suspension by firefly luciferase luminescence.
Academic Article Continuous measurement and rapid kinetics of ATP synthesis in rat liver mitochondria, mitoplasts and inner membrane vesicles determined by firefly-luciferase luminescence.
Academic Article Lateral diffusion of ubiquinone during electron transfer in phospholipid- and ubiquinone-enriched mitochondrial membranes.
Academic Article Thermodynamics of reverse electron transfer across site 1: ATP/2e- is greater than one.
Academic Article The ATP-to-oxygen stoichiometries of oxidative phosphorylation by rat liver mitochondria. An analysis of ADP-induced oxygen jumps by linear nonequilibrium thermodynamics.
Academic Article Fusion of liposomes with mitochondrial inner membranes.
Academic Article Cyclophilin D as a drug target.
Academic Article Role of the mitochondrial permeability transition in apoptotic and necrotic death after ischemia/reperfusion injury to hepatocytes.
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 Contribution of the mitochondrial permeability transition to lethal injury after exposure of hepatocytes to t-butylhydroperoxide.
Academic Article Novel mechanisms in chemically induced hepatotoxicity.
Academic Article Distribution of electrical potential, pH, free Ca2+, and volume inside cultured adult rabbit cardiac myocytes during chemical hypoxia: a multiparameter digitized confocal microscopic study.
Academic Article Measurement of electrical potential, pH, and free calcium ion concentration in mitochondria of living cells by laser scanning confocal microscopy.
Academic Article The mitochondrial permeability transition: a new pathophysiological mechanism for Reye's syndrome and toxic liver injury.
Academic Article Synergism of cyclosporin A and phospholipase inhibitors in protection against lethal injury to rat hepatocytes from oxidant chemicals.
Academic Article Cyclosporin A delays mitochondrial depolarization induced by N-methyl-D-aspartate in cortical neurons: evidence of the mitochondrial permeability transition.
Academic Article Mitochondrial permeability transition in hepatocytes induced by t-BuOOH: NAD(P)H and reactive oxygen species.
Academic Article Rusty notions of cell injury.
Academic Article The mitochondrial permeability transition in toxic, hypoxic and reperfusion injury.
Academic Article Primary cirrhotic hepatocytes resist TGFbeta-induced apoptosis through a ROS-dependent mechanism.
Academic Article Nitric oxide protects rat hepatocytes against reperfusion injury mediated by the mitochondrial permeability transition.
Academic Article Nitric oxide: a signaling molecule against mitochondrial permeability transition- and pH-dependent cell death after reperfusion.
Academic Article Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging.
Academic Article Dephosphorylation of the Rieske iron-sulfur protein after induction of the mitochondrial permeability transition.
Academic Article Peroxynitrite-induced mitochondrial and endonuclease-mediated nuclear DNA damage in acetaminophen hepatotoxicity.
Academic Article Voltage-dependent anion channel (VDAC) as mitochondrial governator--thinking outside the box.
Academic Article Apoptosis and necrosis in the liver: a tale of two deaths?
Academic Article Calcium and pH in anoxic and toxic injury.
Academic Article Nuclear translocation of endonuclease G and apoptosis-inducing factor during acetaminophen-induced liver cell injury.
Academic Article Inhibition of mitochondrial respiration as a source of adaphostin-induced reactive oxygen species and cytotoxicity.
Academic Article Imaging of mitochondrial polarization and depolarization with cationic fluorophores.
Academic Article NIM811, a mitochondrial permeability transition inhibitor, prevents mitochondrial depolarization in small-for-size rat liver grafts.
Academic Article Selective degradation of mitochondria by mitophagy.
Academic Article Modulation of mitochondrial membrane permeability in pathogenesis, autophagy and control of metabolism.
Academic Article Mitochondrial bax translocation accelerates DNA fragmentation and cell necrosis in a murine model of acetaminophen hepatotoxicity.
Academic Article Transforming growth factor beta mediates hepatocyte apoptosis through Smad3 generation of reactive oxygen species.
Academic Article Minocycline and N-methyl-4-isoleucine cyclosporin (NIM811) mitigate storage/reperfusion injury after rat liver transplantation through suppression of the mitochondrial permeability transition.
Academic Article UCPs--unlikely calcium porters.
Academic Article Is there release of mitochondrial calcium in toxic injury?
Academic Article Mitochondrial calcium and the permeability transition in cell death.
Academic Article c-Jun N-terminal kinase modulates oxidant stress and peroxynitrite formation independent of inducible nitric oxide synthase in acetaminophen hepatotoxicity.
Academic Article The oxygen tension modulates acetaminophen-induced mitochondrial oxidant stress and cell injury in cultured hepatocytes.
Academic Article Inhibition of the mitochondrial permeability transition by protein kinase A in rat liver mitochondria and hepatocytes.
Academic Article Apoptosis-inducing factor modulates mitochondrial oxidant stress in acetaminophen hepatotoxicity.
Academic Article Lysosomal signaling enhances mitochondria-mediated photodynamic therapy in A431 cancer cells: role of iron.
Academic Article Autophagy in alcohol-induced liver diseases.
Academic Article Role of inducible nitric oxide synthase in mitochondrial depolarization and graft injury after transplantation of fatty livers.
Academic Article Warburg revisited: regulation of mitochondrial metabolism by voltage-dependent anion channels in cancer cells.
Academic Article Voltage-dependent anion channels modulate mitochondrial metabolism in cancer cells: regulation by free tubulin and erastin.
Academic Article Alkyltin inhibition of ATPase activities in tissue homogenates and subcellular fractions from adult and neonatal rats.
Academic Article Oxidative phosphorylation and ultrastructural transformation in mitochondria in the intact ascites tumor cell.
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.
Academic Article Non-equilibrium thermodynamics of oxidative phosphorylation by inverted inner membrane vesicles of rat liver mitochondria.
Academic Article Near thermodynamic equilibrium of oxidative phosphorylation by inverted inner membrane vesicles of rat liver mitochondria.
Academic Article Progression of subcellular changes during chemical hypoxia to cultured rat hepatocytes: a laser scanning confocal microscopic study.
Academic Article ATP depletion rather than mitochondrial depolarization mediates hepatocyte killing after metabolic inhibition.
Academic Article Mitochondria as a source of reactive oxygen species during reductive stress in rat hepatocytes.
Academic Article Mitochondrial and glycolytic dysfunction in lethal injury to hepatocytes by t-butylhydroperoxide: protection by fructose, cyclosporin A and trifluoperazine.
Academic Article Mitochondrial free calcium transients during excitation-contraction coupling in rabbit cardiac myocytes.
Academic Article Selective loading of Rhod 2 into mitochondria shows mitochondrial Ca2+ transients during the contractile cycle in adult rabbit cardiac myocytes.
Concept Mitochondria
Concept Mitochondria, Liver
Concept Mitochondria, Heart
Concept Mitochondria, Muscle
Academic Article Imaging of mitochondrial pH using SNARF-1.
Academic Article Minocycline and doxycycline, but not other tetracycline-derived compounds, protect liver cells from chemical hypoxia and ischemia/reperfusion injury by inhibition of the mitochondrial calcium uniporter.
Academic Article Acute ethanol causes hepatic mitochondrial depolarization in mice: role of ethanol metabolism.
Academic Article Carbenoxolone induces permeability transition pore opening in rat mitochondria via the translocator protein TSPO and connexin43.
Academic Article Variants of mitochondrial autophagy: Types 1 and 2 mitophagy and micromitophagy (Type 3).
Academic Article ATP/ADP ratio, the missed connection between mitochondria and the Warburg effect.
Academic Article ATP/ADP Turnover and Import of Glycolytic ATP into Mitochondria in Cancer Cells Is Independent of the Adenine Nucleotide Translocator.
Academic Article Translocation of iron from lysosomes to mitochondria during acetaminophen-induced hepatocellular injury: Protection by starch-desferal and minocycline.
Academic Article The mitochondria-targeted antioxidant MitoQ attenuates liver fibrosis in mice.
Academic Article Low Dose Acetaminophen Induces Reversible Mitochondrial Dysfunction Associated with Transient c-Jun N-Terminal Kinase Activation in Mouse Liver.
Academic Article Combined effect of G3139 and TSPO ligands on Ca(2+)-induced permeability transition in rat brain mitochondria.
Academic Article Disrupted Renal Mitochondrial Homeostasis after Liver Transplantation in Rats.
Academic Article Signaling From Lysosomes Enhances Mitochondria-Mediated Photodynamic Therapy In Cancer Cells.
Academic Article Effect of the CRAC Peptide, VLNYYVW, on mPTP Opening in Rat Brain and Liver Mitochondria.
Academic Article Compartmentation of Mitochondrial and Oxidative Metabolism in Growing Hair Follicles: A Ring of Fire.
Academic Article 2',3'-Cyclic nucleotide 3'-phosphodiesterase as a messenger of protection of the mitochondrial function during melatonin treatment in aging.
Academic Article Glutamate contributes to alcohol hepatotoxicity by enhancing oxidative stress in mitochondria.
Academic Article ATP/ADP turnover and import of glycolytic ATP into mitochondria in cancer cells is independent of the adenine nucleotide translocator.
Academic Article HDAC1 localizes to the mitochondria of cardiac myocytes and contributes to early cardiac reperfusion injury.
Academic Article Acid sphingomyelinase promotes mitochondrial dysfunction due to glutamate-induced regulated necrosis.
Academic Article Erastin-Like Anti-Warburg Agents Prevent Mitochondrial Depolarization Induced by Free Tubulin and Decrease Lactate Formation in Cancer Cells.
Academic Article Imaging of Mitochondrial pH Using SNARF-1.
Academic Article Mitochondrial protein import is regulated by p17/PERMIT to mediate lipid metabolism and cellular stress.
Academic Article JNK activation and translocation to mitochondria mediates mitochondrial dysfunction and cell death induced by VDAC opening and sorafenib in hepatocarcinoma cells.
Academic Article Suppression of iron mobilization from lysosomes to mitochondria attenuates liver injury after acetaminophen overdose in vivo in mice: Protection by minocycline.
Academic Article Aldehyde dehydrogenase-2 activation decreases acetaminophen hepatotoxicity by prevention of mitochondrial depolarization.
Academic Article The role of Iron in lipid peroxidation and protein nitration during acetaminophen-induced liver injury in mice.
Academic Article A new fluorescent sensor mitoferrofluor indicates the presence of chelatable iron in polarized and depolarized mitochondria.
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  • Mitochondria