Department of biochemistry and Molecular biology
John Lemasters, MD, PhD
Departments of Biochemistry & Molecular Biology and Pharmaceutical Sciences
Director, Center for Cell Death, Injury and Regeneration
1975 Ph.D Cell Biology, Johns Hopkins University
1975 M.D, Johns Hopkins University
1969 B.A., Psychology, Yale University
My research interests relate to mitochondrial and cellular bioenergetics, including studies of oxidative phosphorylation in isolated mitochondria, mitochondrial dysfunction in toxic, hypoxic and reperfusion injury to hepatocytes, cardiac myocytes and organs stored for transplantation surgery, and control of metabolism. 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 mitochondrial permeability transition (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. 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 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. 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 tissues.
1. Lemasters, J.J. (2013) Hepatotoxicity due to mitochondrial injury. In Drug-Induced Liver Disease, 3rd Ed., N. Kaplowitz and L. DeLeve (Eds.), Elsevier, Amsterdam, pp.85-100.
2. Maldonado, E.N., K.L. Sheldon, D.N. DeHart, J. Patnaik, Y. Manevich, D.M. Townsend, S.M. Bezrukov, T.K. Rostovtseva and J.J. Lemasters (2013) Voltage dependent anion channels modulate mitochondrial metabolism in cancer cells: regulation by free tubulin and erastin. J. Biol. Chem. 288, 11920-11929. PMCID: PMC3636879.
3. Zhang, X., and J.J. Lemasters (2013) Translocation of iron from lysosomes to mitochondria during ischemia predisposes to injury after reperfusion in rat hepatocytes. Free Rad. Biol. Med. 63, 243–253. PMCID in process.
4. Kholmukhamedov, A, J.M. Schwartz and J.J. Lemasters (2013) Isolated mitochondria infusion mitigates ischemia-reperfusion injury of the liver in rats: mitotracker probes and mitochondrial membrane potential. Shock 39, 543. PMCID in process.
5. Hung, H.-I., J.M. Schwartz, E.N. Maldonado, J.J. Lemasters and A.-L. Nieminen (2013) Mitoferrin-2-dependent mitochondrial iron uptake sensitizes human head and neck squamous carcinoma cells to photodynamic therapy. J. Biol. Chem. 288, 677-686. PMCID: PMC3537066.
6. Ramshesh, V.K. and J.J. Lemasters (2012) Imaging of mitochondrial pH using SNARF-1. In Mitochondrial Bioenergetics: Methods and Protocols, C. Palmeira and A. Moreno, Eds., Meth. Mol Biol. 810, 243-248. PMCID in process.
7. Kim, J.-S., J.H. Wang and J.J. Lemasters (2012) Mitochondrial permeability transition in rat hepatocytes after anoxia/reoxygenation: role of Ca2+-dependent mitochondrial formation of reactive oxygen species. Am. J. Physiol. 302, G723-G731. PMCID: PMC3330780.
8. Lemasters, J.J., E.L. Holmuhamedov, C. Czerny, Z. Zhong and E.N. Maldonado (2012) Regulation of mitochondrial function by voltage dependent anion channels in ethanol metabolism and the Warburg effect. Biochim. Biophys. Acta 1818, 1536-1544. PMCID: PMC3422743.
9. Czerny, C., T.P. Theruvath, E. Maldonado, M. Lehnert, I. Marzi, Z. Zhong and J.J. Lemasters (2012) c-Jun N-terminal kinase 2 promotes liver injury via the mitochondrial permeability transition after hemorrhage and resuscitation. HPB Surgery 2012, 641982. PMCID: PMC3390051.
10. Czerny, C., A. Kholmukhamedov, T.P. Theruvath, E. Maldonado, V.K. Ramshesh, M. Lehnert, I. Marzi, Z. Zhong and J.J. Lemasters (2012) Minocycline decreases liver injury after hemorrhagic shock and resuscitation in mice. HPB Surgery 2012, 259512. PMCID: PMC3375163.
11. Theruvath, T.P., V.K. Ramshesh, Z. Zhong, R.T. Currin, T. Karrasch and J.J. Lemasters (2012) ICAM-1 upregulation in ethanol-induced fatty murine livers promotes injury and sinusoidal leukocyte adherence after transplantation. HPB Surgery 2012, 480893. PMCID: PMC3385666.
12. Liu, Q, H. Rehman, Y. Krishnasamy, V.K. Ramshesh, T.P. Theruvath, K.D. Chavin, R.G. Schnellmann, J.J. Lemasters, and Z. Zhong (2012) Role of inducible nitric oxide synthase in mitochondrial depolarization and graft injury after transplantation of fatty livers. Free Radic. Biol. Med. 56, 250-259. PMCID: PMC3392495.
13. Holmuhamedov, E.L., C. Czerny, C.C. Beeson and J.J. Lemasters (2012) Ethanol suppresses ureagenesis in rat hepatocytes: role of acetaldehyde. J. Biol. Chem. 287, 7692-76700. PMCID: PMC3293599.
14. Dolganiuc, A., P.G. Thomes, W.-X. Ding, J.J. Lemasters and T.M. Donohue (2012) Autophagy in alcohol-induced liver diseases. Alcohol. Clin. Exp. Res. 36, 1301-1308. PMCID PMC3653416.
15. Maldonado, E.N. and J.J. Lemasters (2012) Warburg revisited: regulation of mitochondrial metabolism by voltage dependent anion channels in cancer cells. J. Pharmacol. Exp. Therapeut. 342, 637-641. PMCID: PMC3422523.