Fluorescent Reporters of Mitochondrial Function in the Life and Death of Cells

Webinar Abstract:

My research is focused on the cellular and molecular mechanisms underlying hypoxic and toxic injury to liver and heart cells and organs stored for transplantation surgery.

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 and anoxia, cytopathic hypoxia of sepsis and multiple organ failure, alcoholic liver disease, aerobic glycolysis in cancer cells (Warburg effect) and unstimulated pancreatic beta cells.

Join us for this 45-minute webinar to learn how to employ technologies that utilize fluorescent probes to measure mitochondrial membrane potential, membrane permeability, reactive oxygen and nitrogen species, ions, redox state, biogenesis and turnover.

You will learn:

• How to use fluorescent reporters to monitor mitochondria function both of isolated mitochondria and mitochondria in live cells and animals.
• How these probes are employed to assess the role of mitochondria in cell death pathways and in comparison to respiratory function.

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Originally presented Wednesday, February 18, 2009

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References and Additional Links:

Center for Cell Death, Injury & Regeneration

MUSC/Seahorse Bioscience Academic Core Facility

Guest Speaker Contact Information:

John J. Lemasters, M.D., Ph.D
Director and Professor,
Center for Cell Death, Injury and Regeneration
DepartmentsofPharmaceutical& Biomedical Sciences and Biochemistry &MolecularBiology
Medical University of South Carolina, Charleston, SC
Email:JJLemasters@musc.edu

Selected Publications by John J. Lemasters:

Zhong, Z., V.K. Ramshesh, H. Rehman, R.T. Currin, V.Sridharan, T.P. Theruvath, I. Kim, G.L. Wright and J.J. Lemasters (2008) Activation of the oxygen-sensing signal cascade prevents mitochondrial injury after mouse liver ischemia-reperfusion. American Journal of Physiology, in press

Ramshesh, V.K., and J.J. Lemasters (2008) Luminescence lifetime imaging microscopy by confocal pinhole shifting (LLIM-CPS). Journal of Biomedical Optics, in press.

Uchiyama,A., J.-S. Kim, K. Kon, H. Jaeschke, K. Ikejima, S. Watanabe and J.J. Lemasters (2008) Translocation of iron from lysosomes into mitochondria is a key event during oxidative stress-induced hepatocellular injury. Hepatology, in press.

Theruvath, T.P. C. Czerny, V.K. Ramshesh, Z. Zhong, K.D. Chavin, and J.J. Lemasters (2008) c-Jun N-terminal kinase 2 promotes graft injury via the mitochondrial permeability transition after mouse liver transplantation. Am. J. Transplant.8, 1819"“1828.

Theruvath, T.P., M.C. Snoddy, Z. Zhong, and J.J. Lemasters (2008)Mitochondrial permeability transition in liver ischemia and reperfusion: role of c-Jun N-terminal kinase 2. Transplanation85, 1500-1504.

Theruvath, T.P., Z. Zhong, P. Pediaditakis, V.K. Ramshesh, R.T. Currin, A. Tikunov, E. Holmuhamedov and J.J. Lemasters (2008) Minocycline and N-methyl-4-isoleucine cyclosporin (NIM811) mitigate storage/reperfusion injury after rat liver transplantation through suppression of the mitochondrial permeability transition. Hepatology47, 236-246.

Lemasters, J.J., and V.K. Ramshesh (2007) Imaging of mitochondrial polarization and depolarization with cationic fluorophores. Meth. Cell Biol. 80, 283-295.

Zhong, Z., T.P. Theruvath, R.T. Currin, P.C. Waldmeier and J.J. Lemasters (2007) NIM811, a mitochondrial permeability transition inhibitor, prevents mitochondrial depolarization in small-for-size rat liver grafts. Am. J. Transplant.7, 1103-1111.

Kim, I., S. Rodriguez-Enriquez and J.J. Lemasters (2007) Selective degradation of mitochondria by mitophagy. Arch. Biochem. Biophys. 462 , 245"“253.

Malhi, H., G.J. Gores and J.J. Lemasters (2006) Apoptosis and necrosis in the liver: a tale of two deaths? Hepatology 43, S31-S44.

Conzelmann, L.O., M. Lehnert, M. Kremer, Z. Zhong, M.D. Wheeler, and J.J. Lemasters (2006) Graft tumor necrosis factor receptor 1 protects after mouse liver transplantation whereas host TNFR1 promotes injury. Transplantation 82, 1214-1220.

Lehnert, M., T. Uehara, B.U. Bradford, H. Lind, Z. Zhong, D.A. Brenner, I. Marzi | and J.J. Lemasters (2006) Lipopolysaccharide-binding protein modulates hepatic damage and the intracellular stress response after hemorrhagic shock and resuscitation. Am. J. Physiol. 291, G456-G463.

Kim, J.-S., Y. Jin, and J.J. Lemasters (2006) Reactive oxygen species, but not Ca 2+, trigger pH- and mitochondrial permeability transition-dependent killing of adult rat myocytes after ischemia/reperfusion. Am. J. Physiol. 290, H2024-H2034.

Vairetti, M., P. Richelmi, F. Bertè, R.T. Currin, J.J. Lemasters, and R. Imberti (2006) Role of pH in protection by low sodium against hypoxic injury in isolated perfused rat livers. J. Hepatol. 44, 894"“901.

Lemasters, J.J., and E. Holmuhamedov (2006) Voltage-dependent anion channel (VDAC) as mitochondrial governator "“ thinking outside the box. Biochim. Biophys. Acta 1762, 181-190.

Rodriguez-Enriquez, S., I. Kim, R.T. Currin and J.J. Lemasters (2006) Tracker dyes to probe mitochondrial autophagy (mitophagy) in rat hepatocytes. Autophagy 2, 39-46.