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Thomas Edgar Gunter, Ph.D.

Thomas Edgar Gunter, Ph.D.

Contact

Office (585) 275-3129
Fax (585) 271-2683

About Me

Faculty Appointments

Professor Emeritus - Department of Biochemistry and Biophysics (SMD)

Credentials

Education

PhD | Univ of Cal Berkeley. Physics. 1966

BS | Mass Inst Technology. Physics. 1960

Research

Until recently, the rate of ATP production was thought to be determined by the rate at which ADP and phosphate (Pi) diffuse back to mitochondria. Recent evidence at the cellular and tissue levels suggests control by a novel mechanism, probably functioning through intramitochondrial [Ca2+]. 31P NMR h...
Until recently, the rate of ATP production was thought to be determined by the rate at which ADP and phosphate (Pi) diffuse back to mitochondria. Recent evidence at the cellular and tissue levels suggests control by a novel mechanism, probably functioning through intramitochondrial [Ca2+]. 31P NMR has identified conditions in which [ADP] and [Pi] remain constant while ATP production is increased by a factor of four or more. Clearly, metabolic rate cannot be activated by increased [ADP] and [Pi] if they do not increase, and another mechanism of control is indicated. This additional mechanism is thought to involve intramitochondrial free calcium ([Ca2+]m). Therefore, it is important to determine whether enough Ca2+ can be sequestered by mitochondria under physiological conditions to serve this function of metabolic mediator (1).

Under physiological conditions, cytosolic free calcium ([Ca2+]c) in many tissues remains low (80 to 100 nM) except during pulses or transients of [Ca2+]c. During these pulses, [Ca2+]c can become 1 µM or larger. Even liver, a non excitable tissue, may respond to hormones through a sequence of Ca2+ pulses. A typical hepatocyte response to vasopressin, for example, could be a sequence of 6 or 8 Ca2+ pulses. It is important to determine if mitochondria can sequester enough Ca2+ from such pulses to activate the Ca2+-sensitive steps of the metabolic pathways (1). Calculations based on the kinetics of known mitochondrial Ca2+ transporters suggested that they cannot sequester enough Ca2+(1). However, these kinetics were determined using buffered [Ca2+], not [Ca2+] pulses as under physiological conditions.

We built a device capable of generating Ca2+ pulses like those observed in vivo in many tissues. The [Ca2+] is controlled by a computer-controlled automatic pipetter and measured using fluorescence. We can generate [Ca2+] pulses down to durations of 0.2 - 0.3 sec. over a broad range of [Ca2+]. Using this device, we have discovered a new mechanism of Ca2+ uptake into liver mitochondria, termed the RaM ("rapid mechanism"). Controls show that the RaM mediates rapid net mitochondrial uptake from Ca2+ pulses (2). The RaM briefly displays very high Ca2+ conductivity at the beginning of a pulse; however, the RaM is rapidly closed as the [Ca2+] of the pulse increases. It is quickly "reset" by the fall in [Ca2+] between Ca2+ pulses and therefore functions at the beginning of each pulse. It is sufficiently activated by physiological concentrations of spermine to allow enough Ca2+ to be sequestered from a few pulses to stimulate ATP production. RaM-mediated metabolic signaling shows characteristics of "frequency modulation" (2). The RaM also exists in heart mitochondria; however, its characteristics in heart are quite different from those observed in liver. We believe that this newly discovered mechanism may be the most important component of the system controlling metabolic rate.

Publications

Journal Articles

Manganese neurotoxicity and the role of reactive oxygen species.

Martinez-Finley EJ, Gavin CE, Aschner M, Gunter TE

Free radical biology & medicine.. 2013 September 62 :65-75. Epub 02/08/2013.

Manganese transport via the transferrin mechanism.

Gunter TE, Gerstner B, Gunter KK, Malecki J, Gelein R, Valentine WM, Aschner M, Yule DI

Neurotoxicology.. 2013 January 34 :118-27. Epub 11/09/2012.

An analysis of the effects of Mn2+ on oxidative phosphorylation in liver, brain, and heart mitochondria using state 3 oxidation rate assays.

Gunter TE, Gerstner B, Lester T, Wojtovich AP, Malecki J, Swarts SG, Brookes PS, Gavin CE, Gunter KK

Toxicology and applied pharmacology.. 2010 November 15249 (1):65-75. Epub 08/26/2010.

Characteristics and possible functions of mitochondrial Ca(2+) transport mechanisms.

Gunter TE, Sheu SS

Biochimica et biophysica acta.. 2009 November 1787 (11):1291-308. Epub 01/06/2009.

The case for manganese interaction with mitochondria.

Gunter TE, Gavin CE, Gunter KK

Neurotoxicology.. 2009 July 30 (4):727-9. Epub 05/22/2009.

Cyclophilin D interacts with Bcl2 and exerts an anti-apoptotic effect.

Eliseev RA, Malecki J, Lester T, Zhang Y, Humphrey J, Gunter TE

The Journal of biological chemistry.. 2009 April 10284 (15):9692-9. Epub 02/19/2009.

Nanoparticle (NP) uptake by type I alveolar epithelial cells and their oxidant stress response.

Vanwinkle BA, de Mesy Bentley KL, Malecki JM, Gunter KK, Evans IM, Elder A, Finkelstein JN, Oberdörster G, Gunter TE

Nanotoxicology.. 2009 January 13 (4):307-318. Epub 1900 01 01.

UCPs--unlikely calcium porters.

Brookes PS, Parker N, Buckingham JA, Vidal-Puig A, Halestrap AP, Gunter TE, Nicholls DG, Bernardi P, Lemasters JJ, Brand MD

Nature cell biology.. 2008 November 10 (11):1235-7; author reply 1237-40. Epub 1900 01 01.

Role of cyclophilin D in the resistance of brain mitochondria to the permeability transition.

Eliseev RA, Filippov G, Velos J, VanWinkle B, Goldman A, Rosier RN, Gunter TE

Neurobiology of aging.. 2007 October 28 (10):1532-42. Epub 07/31/2006.

Determining the oxidation states of manganese in NT2 cells and cultured astrocytes.

Gunter KK, Aschner M, Miller LM, Eliseev R, Salter J, Anderson K, Gunter TE

Neurobiology of aging.. 2006 December 27 (12):1816-26. Epub 11/14/2005.

Speciation of manganese in cells and mitochondria: a search for the proximal cause of manganese neurotoxicity.

Gunter TE, Gavin CE, Aschner M, Gunter KK

Neurotoxicology.. 2006 September 27 (5):765-76. Epub 05/07/2006.

Determining the oxidation states of manganese in PC12 and nerve growth factor-induced PC12 cells.

Gunter KK, Aschner M, Miller LM, Eliseev R, Salter J, Anderson K, Hammond S, Gunter TE

Free radical biology & medicine.. 2005 July 1539 (2):164-81. Epub 03/31/2005.

Diazoxide-mediated preconditioning against apoptosis involves activation of cAMP-response element-binding protein (CREB) and NFkappaB.

Eliseev RA, Vanwinkle B, Rosier RN, Gunter TE

The Journal of biological chemistry.. 2004 November 5279 (45):46748-54. Epub 08/23/2004.

Calcium and mitochondria.

Gunter TE, Yule DI, Gunter KK, Eliseev RA, Salter JD

FEBS letters.. 2004 June 1567 (1):96-102. Epub 1900 01 01.

Determination of the oxidation states of manganese in brain, liver, and heart mitochondria.

Gunter TE, Miller LM, Gavin CE, Eliseev R, Salter J, Buntinas L, Alexandrov A, Hammond S, Gunter KK

Journal of neurochemistry.. 2004 January 88 (2):266-80. Epub 1900 01 01.

Bcl-2 prevents abnormal mitochondrial proliferation during etoposide-induced apoptosis.

Eliseev RA, Gunter KK, Gunter TE

Experimental cell research.. 2003 October 1289 (2):275-81. Epub 1900 01 01.

Bcl-2 and tBid proteins counter-regulate mitochondrial potassium transport.

Eliseev RA, Salter JD, Gunter KK, Gunter TE

Biochimica et biophysica acta.. 2003 April 181604 (1):1-5. Epub 1900 01 01.

Parathyroid hormone-related peptide regulation of chick tibial growth plate chondrocyte maturation requires protein kinase A.

Zuscik MJ, O'Keefe RJ, Gunter TE, Puzas JE, Schwarz EM, Rosier RN

Journal of orthopaedic research : official publication of the Orthopaedic Research Society.. 2002 September 20 (5):1079-90. Epub 1900 01 01.

Growth plate chondrocyte maturation is regulated by basal intracellular calcium.

Zuscik MJ, D'Souza M, Ionescu AM, Gunter KK, Gunter TE, O'Keefe RJ, Schwarz EM, Puzas JE, Rosier RN

Experimental cell research.. 2002 June 10276 (2):310-9. Epub 1900 01 01.

Bcl-2 sensitive mitochondrial potassium accumulation and swelling in apoptosis.

Eliseev RA, Gunter KK, Gunter TE

Mitochondrion.. 2002 February 1 (4):361-70. Epub 1900 01 01.

XANES spectroscopy: A Promising tool for toxicology: A tutorial

Gunter, K. K.; Miller, L.M.; Aschner, M.; Eliseev, R.; Depuis, D.; Gavin, C. E.; Gunter, T. E.;.

Neurotox. 2002; 23(3): 127 146.

Measurements of intracellular free calcium concentration in biological systems.

Gunter KK, Gunter TE

Current protocols in toxicology. 2001 May Chapter 2 :Unit 2.5. Epub 1900 01 01.

The rapid mode of calcium uptake into heart mitochondria (RaM): comparison to RaM in liver mitochondria.

Buntinas L, Gunter KK, Sparagna GC, Gunter TE

Biochimica et biophysica acta.. 2001 April 21504 (2-3):248-61. Epub 1900 01 01.

Uptake of calcium by mitochondria: transport and possible function.

Gunter TE, Gunter KK

IUBMB life.. 2001 52 (3-5):197-204. Epub 1900 01 01.

Release of Ca2+ from mitochondria via the saturable mechanisms and the permeability transition.

Pfeiffer DR, Gunter TE, Eliseev R, Broekemeier KM, Gunter KK

IUBMB life.. 2001 52 (3-5):205-12. Epub 1900 01 01.

Mitochondrial calcium transport: mechanisms and functions.

Gunter TE, Buntinas L, Sparagna G, Eliseev R, Gunter K

Cell calcium.. 2000 28 (5-6):285-96. Epub 1900 01 01.

Measurements of intracellular free calcium concentration in biological systems

Gunter, K.K.; Gunter, T. E.;.

Current Protocols in Toxicology; M. Maines, L.G. Costa, D. J. Reed, S. Sassa, and I. G. Sipes, eds; John Wiley & Sons; New York, New York. 1999; : pp 2.5.1 - 2.5.53.

Manganese and calcium transport in mitochondria: implications for manganese toxicity.

Gavin CE, Gunter KK, Gunter TE

Neurotoxicology.. 1999 20 (2-3):445-53. Epub 1900 01 01.

The Ca2+ transport mechanisms of mitochondria and Ca2+ uptake from physiological-type Ca2+ transients.

Gunter TE, Buntinas L, Sparagna GC, Gunter KK

Biochimica et biophysica acta.. 1998 August 101366 (1-2):5-15. Epub 1900 01 01.

PTH and PTHrp effects on growth plate chondrocytes: an overview

Reynolds, S. D.; Zuscik, M. J.; Gunter,T. E.; O'Keefe, R. J.; Puzas, J. E.; Rosier , R. N.; Reynolds, P. R. ;.

In: Cells and Materials. 1998; 7(3): 289 - 300.

The interaction of mitochondria with pulses of calcium.

Gunter TE, Buntinas L, Sparagna GC, Gunter KK

BioFactors.. 1998 8 (3-4):205-7. Epub 1900 01 01.

Characterization of voltage-sensitive calcium channels in growth plate chondrocytes.

Zuscik MJ, Gunter TE, Puzas JE, Rosier RN

Biochemical and biophysical research communications.. 1997 May 19234 (2):432-8. Epub 1900 01 01.

Manganese dynamics in brain mitochondria

Gavin, C. E.; Gunter, T. E.;.

In: Mineral and Metal Neurotoxicology, edited by M. Yasui, K. Ota, M. J. Strong and M. A. Verity. Boca Raton & New York: CRC Press. 1997; : p. 305-310.

Mitochondrial calcium uptake from physiological-type pulses of calcium. A description of the rapid uptake mode.

Sparagna GC, Gunter KK, Sheu SS, Gunter TE

The Journal of biological chemistry.. 1995 November 17270 (46):27510-5. Epub 1900 01 01.

Recurrence of calcium transients in rat cardiomyocytes induced by electrical stimulation in calcium-free Tyrode's solution

Li, K.-X.; Williford, D.; Gunter, T.; Sheu, S.-S. ;.

Biophys. J. 1995; 68(3): a178.

Cyclic-AMP-dependent protein kinase activity is not required by parathyroid hormone to stimulate phosphoinositide signaling in chondrocytes but is required to transduce the hormone's proliferative effect.

Zuscik MJ, Puzas JE, Rosier RN, Gunter KK, Gunter TE

Archives of biochemistry and biophysics.. 1994 December 315 (2):352-61. Epub 1900 01 01.

Cation transport by mitochondria.

Gunter TE

Journal of bioenergetics and biomembranes.. 1994 October 26 (5):465-9. Epub 1900 01 01.

Transport of calcium by mitochondria.

Gunter KK, Gunter TE

Journal of bioenergetics and biomembranes.. 1994 October 26 (5):471-85. Epub 1900 01 01.

Activation of phosphoinositide metabolism by parathyroid hormone in growth plate chondrocytes.

Zuscik MJ, Gunter TE, Rosier RN, Gunter KK, Puzas JE

Cell calcium.. 1994 August 16 (2):112-22. Epub 1900 01 01.

Mitochondrial calcium transport: physiological and pathological relevance.

Gunter TE, Gunter KK, Sheu SS, Gavin CE

The American journal of physiology.. 1994 August 267 (2 Pt 1):C313-39. Epub 1900 01 01.

A system for producing and monitoring in vitro calcium pulses similar to those observed in vivo.

Sparagna GC, Gunter KK, Gunter TE

Analytical biochemistry.. 1994 May 15219 (1):96-103. Epub 1900 01 01.

Na(+)-dependent Ca2+ efflux mechanism of heart mitochondria is not a passive Ca2+/2Na+ exchanger.

Baysal K, Jung DW, Gunter KK, Gunter TE, Brierley GP

The American journal of physiology.. 1994 March 266 (3 Pt 1):C800-8. Epub 1900 01 01.

Can mitochondria sequester pulses from physiological calcium pulses?

Sparagna, G.; Gunter, K. K.; Sheu, S.-S. Gunter, T. E.;.

In: What is Controlling Life?, edited by E. Gnaiger, F. N. Gellerich and M. Wyss. Innsbruck, Austria: Innsbruck Univ. Press. 1994; : p. 154-158.

Mn2+ sequestration by mitochondria and inhibition of oxidative phosphorylation.

Gavin CE, Gunter KK, Gunter TE

Toxicology and applied pharmacology.. 1992 July 115 (1):1-5. Epub 1900 01 01.

The Na(+)-independent Ca2+ efflux mechanism of liver mitochondria is not a passive Ca2+/2H+ exchanger.

Gunter KK, Zuscik MJ, Gunter TE

The Journal of biological chemistry.. 1991 November 15266 (32):21640-8. Epub 1900 01 01.

Mn2+ transport across biological membranes may be monitored spectroscopically using the Ca2+ indicator dye antipyrylazo III.

Gavin CE, Gunter KK, Gunter TE

Analytical biochemistry.. 1991 January 192 (1):44-8. Epub 1900 01 01.

Cytosolic free calcium concentrations in avian growth plate chondrocytes.

Gunter TE, Zuscik MJ, Puzas JE, Gunter KK, Rosier RN

Cell calcium.. 1990 August 11 (7):445-57. Epub 1900 01 01.

Mechanisms by which mitochondria transport calcium.

Gunter TE, Pfeiffer DR

The American journal of physiology.. 1990 May 258 (5 Pt 1):C755-86. Epub 1900 01 01.

Manganese and calcium efflux kinetics in brain mitochondria. Relevance to manganese toxicity.

Gavin CE, Gunter KK, Gunter TE

The Biochemical journal.. 1990 March 1266 (2):329-34. Epub 1900 01 01.

Conversion of esterified fura-2 and indo-1 to Ca2+-sensitive forms by mitochondria.

Gunter TE, Restrepo D, Gunter KK

The American journal of physiology.. 1988 September 255 (3 Pt 1):C304-10. Epub 1900 01 01.

Mechanisms of mitochondrial calcium transport.

Gunter TE, Wingrove DE, Banerjee S, Gunter KK

Advances in experimental medicine and biology.. 1988 232 :1-14. Epub 1900 01 01.

Kinetics of mitochondrial calcium transport. II. A kinetic description of the sodium-dependent calcium efflux mechanism of liver mitochondria and inhibition by ruthenium red and by tetraphenylphosphonium.

Wingrove DE, Gunter TE

The Journal of biological chemistry.. 1986 November 15261 (32):15166-71. Epub 1900 01 01.

Kinetics of mitochondrial calcium transport. I. Characteristics of the sodium-independent calcium efflux mechanism of liver mitochondria.

Wingrove DE, Gunter TE

The Journal of biological chemistry.. 1986 November 15261 (32):15159-65. Epub 1900 01 01.

The efficiencies of the component steps of oxidative phosphorylation. I. A simple steady state theory.

Gunter TE, Jensen BD

Archives of biochemistry and biophysics.. 1986 July 248 (1):289-304. Epub 1900 01 01.

The efficiencies of the component steps of oxidative phosphorylation. II. Experimental determination of the efficiencies in mitochondria and examination of the equivalence of membrane potential and pH gradient in phosphorylation.

Jensen BD, Gunter KK, Gunter TE

Archives of biochemistry and biophysics.. 1986 July 248 (1):305-23. Epub 1900 01 01.

Glucagon effects on the membrane potential and calcium uptake rate of rat liver mitochondria.

Wingrove DE, Amatruda JM, Gunter TE

The Journal of biological chemistry.. 1984 August 10259 (15):9390-4. Epub 1900 01 01.

Mechanism of sodium independent calcium efflux from rat liver mitochondria.

Gunter TE, Chace JH, Puskin JS, Gunter KK

Biochemistry.. 1983 December 2022 (26):6341-51. Epub 1900 01 01.

Characterization of the submandibular gland microsomal calcium transport system.

Terman BI, Gunter TE

Biochimica et biophysica acta.. 1983 April 21730 (1):151-60. Epub 1900 01 01.

A method of resuspending small vesicles separated from suspension by protamine aggregation and centrifugation.

Gunter KK, Gunter TE, Jarkowski A, Rosier RN

Analytical biochemistry.. 1982 February 120 (1):113-24. Epub 1900 01 01.

Ca2+ transport against its electrochemical gradient in cytochrome oxidase vesicles reconstituted with mitochondrial hydrophobic proteins.

Rosier RN, Tucker DA, Meerdink S, Jain I, Gunter TE

Archives of biochemistry and biophysics.. 1981 September 210 (2):549-64. Epub 1900 01 01.

On the role of inorganic phosphate in divalent-cation sequestration by mitochondria.

Puskin JS, Gunter TE, Coene MT

European journal of biochemistry. 1980 May 106 (2):425-9. Epub 1900 01 01.

Calcium uptake by cytochrome oxidase vesicles.

Rosier RN, Gunter TE

FEBS letters.. 1980 January 1109 (1):99-103. Epub 1900 01 01.

A rapid method for separating small vesicles from suspension.

Rosier RN, Gunter TE, Tucker DA, Gunter KK

Analytical biochemistry.. 1979 July 1596 (2):384-90. Epub 1900 01 01.

Evidence for separate active mitochondrial efflux mechanisms for Ca2+ and Mn2+

Gunter, K. K.; Rosier, R. N.; Tucker, D. A.; Gunter, T. E.;.

In: Calcium Binding Proteins and Cell Function, edited by R.H.Wasserman, R. P. Corradino, E. Carafoli, R. H. Kretsinger, D. H. MacLennan and F. L. Siege. Amsterdam, London, New York: Elsevier/North Holland. 1979; : p. 498-500.

Uptake of calcium and manganese by rat liver submitochondrial particles.

Gunter TE, Rosier RN, Tucker DA, Gunter KK

Annals of the New York Academy of Sciences.. 1978 April 28307 :246-7. Epub 1900 01 01.

Efflux of Ca2+ and Mn2+ from rat liver mitochondria.

Gunter TE, Gunter KK, Puskin JS, Russell PR

Biochemistry.. 1978 January 2417 (2):339-45. Epub 1900 01 01.

Factors restricting diffusion of water-soluble spin labels.

Keith AD, Snipes W, Mehlhorn RJ, Gunter T

Biophysical journal.. 1977 September 19 (3):205-18. Epub 1900 01 01.

Evidence for more than one Ca2+ transport mechanism in mitochondria.

Puskin JS, Gunter TE, Gunter KK, Russell PR

Biochemistry.. 1976 August 2415 (17):3834-42. Epub 1900 01 01.

An electron paramagnetic resonance study of Mn2+ uptake by the chick chorioallantoic membrane.

Armbrecht HJ, Gunter TE, Puskin JS, Terepka AR

Biochimica et biophysica acta.. 1976 March 19426 (3):557-69. Epub 1900 01 01.

Energy-dependent Mn2+ and Ca2+ uptake by the embryonic chick chorioallantoic membrane.

Armbrecht HJ, Terepka AR, Gunter TE

Biochimica et biophysica acta.. 1976 March 19426 (3):547-56. Epub 1900 01 01.

Transcellular transport of calcium

Terepka, A. R.; Coleman, J. R.; Armbrecht, H. J.; Gunter, T. E.;.

Symp. Soc. Exp. Biol. 1976; 30(3): 117-140.

The use of electron paramagnetic resonance in studies of free and bound divalent cation: the measurement of membrane potentials in mitochondria.

Gunter TE, Puskin JS

Annals of the New York Academy of Sciences.. 1975 December 30264 :112-23. Epub 1900 01 01.

Quantitative magnetic resonance studies of manganese uptake by mitochondria.

Gunter RE, Puskin JS, Russell PR

Biophysical journal.. 1975 April 15 (4):319-33. Epub 1900 01 01.

Electron paramagnetic resonance of copper ion and manganese ion complexes with the ionophore A23187.

Puskin JS, Gunter TE

Biochemistry.. 1975 January 1414 (1):187-91. Epub 1900 01 01.

Ion and pH gradients across the transport membrane of mitochondria following Mn ++ uptake in the presence of acetate.

Puskin JS, Gunter TE

Biochemical and biophysical research communications.. 1973 April 251 (3):797-803. Epub 1900 01 01.

Evidence for the transport of manganous ion against an activity gradient by mitochondria.

Puskin JS, Gunter TE

Biochimica et biophysica acta.. 1972 September 20275 (3):302-7. Epub 1900 01 01.

Manganous ion as a spin label in studies of mitochondrial uptake of manganese.

Gunter TE, Puskin JS

Biophysical journal.. 1972 June 12 (6):625-35. Epub 1900 01 01.

Pressure dependence of the helix-coil transition temperature for polynucleic acid helices.

Gunter TE, Gunter KK

Biopolymers.. 1972 March 11 (3):667-78. Epub 1900 01 01.

Electron paramagnetic resonance studies of the radiolysis of H2O in the solid state

Gunter, T. E.;.

J. Chem. Phys. 1967; 46(3): 3818-3829.

Proton spin-lattice relaxation in (Nd,La)2Mg3(NO3)12á24H2O in high fields and low temperatures

Gunter, T. E.; Jeffries, C. D;.

Phys. Rev. 1967; 159(3): 290-295.

Electron spin resonance of radicals in irradiated hydrogen-oxygen systems in the solid state

Gunter, T. E.;.

In: Solid State Biophysics, edited by S. J. Wyard. New York: McGraw-Hill Book Co. 1967; : p. 157.

Paramagnetic resonance of OH radical in solids and proton spin-lattice relaxation at high fields and low temperatures

Gunter, T. E.;.

University of California, Berkeley, Calif. 1966; .

EPR STUDIES ON OH RADICAL IDENTIFICATION IN IRRADIATED H2O. UCRL-11387 SUPPL.

GUNTER TE, JEFFRIES CD

UCRL [reports].. 1964 15 :8-13. Epub 1900 01 01.