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.
Liu Q, H Rehman, Y Krishnasamy, RG Schnellmann, JJ Lemasters and Z Zhong. (2015) Improvement of liver injury and survival by JNK2 and iNOS deficiency in liver transplants from cardiac death mice. J Hepatol 63:68-74.
Kholmukhamedov A, C Czerny, J Hu, J Schwartz, Z Zhong and JJ Lemasters. (2014) Minocycline and doxycycline, but not tetracycline, mitigate liver and kidney injury after hemorrhagic shock/resuscitation. Shock 42:256-263. PMCID: PMC4134396.
Lemasters JJ. (2014) Variants of mitochondrial autophagy: Types 1 and 2 mitophagy and micromitophagy (Type 3). Redox Biology 2:749–754. PMCID: PMC4085350.
Maldonado EN and JJ Lemasters. (2014) ATP/ADP ratio, the missed connection between mitochondria and the Warburg effect. Mitochondrion 19(Pt. A):78-84. PMCID: PMC4254332.
Zhong Z, VK Ramshesh, H Rehman, Q Liu, TP Theruvath and JJ Lemasters. (2014) Acute ethanol causes hepatic mitochondrial depolarization in mice: role of ethanol metabolism. PLoS One 9:e91308. PMCID: PMC3950152.
Hung H-I, JM Schwartz, EN Maldonado, JJ 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.
Lemasters JJ. (2013) Hepatotoxicity due to mitochondrial injury. In: Drug-Induced Liver Disease, 3rd Ed, N Kaplowitz and L DeLeve (Eds), Elsevier, Amsterdam, pp.85-100.
Maldonado EN, KL Sheldon, DN DeHart, J Patnaik, Y Manevich, DM Townsend, SM Bezrukov, TK Rostovtseva and JJ 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.
Zhang X, and JJ 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: PMC3932485.
Holmuhamedov EL, C Czerny, CC Beeson and JJ Lemasters. (2012) Ethanol suppresses ureagenesis in rat hepatocytes: role of acetaldehyde. J Biol Chem 287:7692-76700. PMCID: PMC3293599.
Kon K, J-S Kim, A Uchiyama, H Jaeschke and JJ Lemasters. (2010) Lysosomal iron mobilization and induction of the mitochondrial permeability transition in acetaminophen-induced toxicity to mouse hepatocytes. Toxicol Sci 117:101-108. PMCID: PMC2923283.
Maldonado EN, J Patnaik, MR Mullins and JJ Lemasters. (2010) Free tubulin modulates mitochondrial membrane potential in cancer cells. Cancer Res 70:10192-10201. PMCID: PMC3010233.