REFERENCESAlston, T. A., Mela, L. & Bright, H. J. (1977). 3-nitropropionate, the toxic substance of Indigofera, is a suicide inactivator of succinate dehydrogenase. Proc. Natl Acad. Sci., USA, 74, 3767–71
Andreassen, O. A., Ferrante, R. J. & Dedeoglu, A. (2001). Mice with a partial deficiency of manganese superoxide dismutase show increased vulnerability to the mitochondrial toxins malonate, 3-nitropropionic acid, and MPTP. Exp. Neurol., 167, 189–95
Andreeva, N., Khodorov, B., Stelmashook, E.et al. (1991). Inhibition of Na/Ca exchange enhances delayed neuronal deathelicited by glutamate in cerebellar granule cell cultures. Brain Res., 548, 322–5
Ankarcrona, M., Dypbukt, J. M., Bonfoco, E.et al. (1995). Glutamate-induced neuronal death: a succession of necrosis or apoptosis depending on mitochondrial function. Neuron, 15, 961–73
Antonsson, B., Montessuit, S., Sanchez, B. & Martinou, J. C. (2001). Bax is present as a high molecular weight oligomer/complex in the mitochondrial membrane of apoptotic cells. J. Biol. Chem., 276, 11615–23
Astrup, J., Sorensen, P. M. & Sorensen, H. R. (1981). Oxygen and glucose consumption related to Na–K transport in canine brain. Stroke, 12, 726–30
Beal, M. F. (1998). Mitochondrial dysfunction in neurodegenerative diseases. Biochim. Biophys. Act., 1366, 211–23
Beal, M. F., Ferrante, R. J., Henshaw, R.et al. (1993). Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J. Neurosci., 13, 4181–92
Beal, M. F., Ferrante, R. J., Henshaw, R.et al. (1995). 3-Nitropropionic acid neurotoxicity is attenuated in copper/zinc superoxide dismutase transgenic mice. J. Neurochem., 65, 919–22
Bennett, M. C., Mlady, G. W., Fleshner, M. & Rose, G. M. (1996). Synergy between chronic corticosterone and sodium azide treatments in producing a spatial learning deficit and inhibiting cytochrome oxidase activity. Proc. Natl Acad, Sci., USA, 93, 1330–4
Bernardi, P., Broekemeier, K. M. & Pfeiffer, D. R. (1994). Recent progress on regulation of the mitochondrial permeability transition pore: a cyclosperin-sensitive pore in the inner mitochondrial membrane. J. Bioenerg. Biomembr., 26, 509–17
Betarbet, R., Sherer, T. B., Mackenzie, G., Garcia-Osuna, M., Panov, A. V. & Greenamyre, J. T. (2000). Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat. Neurosc., 3, 1301–6
Blaustein, M. P. (1988). Calcium transport and buffering in neurons. Trends Neurosci., 10, 438–43
Bogdanov, M. B., Ferrante, R. J., Mueller, G., Ramos, L. E., Martinou, J. C. & Beal, M. F. (1999). Oxidative stress is attenuated in mice overexpressing BCL-2. Neurosci. Lett., 262, 33–6
Boveris, A. & Turrens, J. F. (1980). Production of superoxide anion by the NADH-dehydrogenase of mammalian mitochondria. In Aspects in Superoxide and Superoxide Dismutase. Developments in Biochemistry, ed. J. V. Bannister and H. A. O. Hill, Vol. 11A, pp. 84–91. New York: Elsevier-North Holland
Boveris, A., Oshino, N. & Chance, B. (1972). The cellular production of hydrogen peroxide. Biochem. J., 128, 617–30
Brouillet, E., Hyman, B. T., Jenkins, B. G.et al. (1994). Systemic or local administration of azide produces striatal lesions by an energy impairment-induced excitotoxic mechanism. Exp. Neurol., 129, 175–82
Brouillet, E., Hantraye, P., Ferrante, R. J.et al. (1995). Chronic mitochondrial energy impairment produces selective striatal degeneration and abnormal choreiform movements in primates. Proc. Natl Acad. Sci., USA, 92, 7105–9
Cao, X. & Phillis, J. W. (1994). Alpha-phenyl-test-butyl nitrone reduces cortical infarct and edema in rats subjected to focal ischemia.Brain Res., 644, 267–72
Carter, A. J., Muller, R. E., Pschorn, U. & Stransky, W. (1995). Preincubation with creatine enhances levels of creatine phosphate and prevents anoxic damage in rat hippocampal slices. J. Neurochem., 64, 2691–9
Cousin, M. A., Nicholls, D. G. & Pocock, J. M. (1995). Modulation of ion gradients and glutamate release in cultured cerebellar granule cells by ouabain. J. Neurochem., 64, 2097–104
Crompton, M. (1999). The mitochondrial permeability transition pore and its role in cell death. Biochem. J., 341, 233–49
Crompton, M., Virji, S. & Ward, J. M. (1998). Cyclophilin-D binds strongly to complexes of the voltage-dependent anion channel and the adenine nucleotide translocase to form the permeability transition pore. Eur. J. Biochem., 258, 729–35
Davey, G. P., Peuchen, S. & Clark, J. B. (1998). Energy thresholds in brain mitochondria. Potential involvement in neurodegeneration. J. Biol. Chem., 273, 12753–7
Ding, H. F. & Fisher, D. E. (1998). Mechanisms of p53-mediated apoptosis. Crit. Rev. Oncol., 9, 83–98
Du, C., Fang, M., Li, Y. & Wang, X. (2000). Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell, 102, 33–42
Ekert, P. G., Silke, J., Hawkins, C. J., Verhagen, A. M. & Vaux, D. L. (2001). DIABLO promotes apoptosis by removing MIHA/XIAP from processed caspase 9. J. Cell Biol., 152, 483–90
Erecinska, M. & Dagani, F. (1990) Relationships between the neuronal sodium/potassium pump and energy metabolism. J. Gen. Physiol., 95, 591–616
Fiskum, G., Murphy, A. N. & Beal, M. F. (1999). Mitochondria in neurodegeneration: acute ischemia and chronic neurodegenerative diseases. J. Cereb. Blood Flow Metab., 19, 351–69
Flint, D. H., Tuminello, J. F. & Emptage, M. H. (1993). The inactivation of Fe-S cluster containing hydro-lases by superoxide. J. Biol. Chem., 268, 22369–76
Fridovitch, I. (1995). Superoxide radical and superoxide dismutases. Ann. Rev. Biochem., 64, 97–112
Greenamyre, J. T., Garcia-Osuna, M. & Greene, J. G. (1994). The endogenous cofactors, thioctic acid and dihydrolipoic acid, are neuroprotective against NMDA and malonic acid lesions of striatum. Neurosci. Lett., 171, 17–20
Greene, J. G. & Greenamyre, J. T. (1995). Characterization of the excitotoxic potential of the reversible succinate dehydrogenase inhibitor malonate. J. Neurochem., 64, 430–6
Greene, J. G. & Greenamyre, J. T. (1996). Manipulation of membrane potential modulates malonate-induced striatal excitotoxicity. J. Neurochem., 66, 637–43
Greene, J. G., Sheu, S. S., Gross, R. A. & Greenamyre, J. T. (1998). 3-nitropropionic acid exacerbates N-methyl-D-aspartate toxicity in striatal culture by multiple mechanisms. Neuroscience, 84, 503–10
Gunasekar, P. G., Kanthasamy, A. G., Borowitz, J. L. & Isom, G. (1995). NMDA receptor activation produces concurrent generation of nitric oxide and reactive oxygen species: implication for cell death. J. Neurochem., 65, 2016–21
Gunter, T. E. & Gunter, K. K. (2001). Uptake of calcium by mitochondria: transport and possible function. IUBMB Life, 52, 197–204
Gunter, T. E., Gunter, K. K., Sheu, S.- S. & Gavin, C. E. (1994). Mitochondrial calcium transport. Am. J. Physiol., 267, C313–39
Hengartner, M. O. (2000). The biochemistry of apoptosis. Nature, 407, 770–6
Hensley, K., Pye, Q. N., Maidt, M.et al. (1998). Interaction of alpha-phenyl-N-tert-butyl nitrone and alternative electron acceptors with complex I indicates a substrate reduction site upstream from the rotenone binding site. J. Neurochem., 71, 2549–57
Hochster R. M. & Quastel J. H., eds. (1963). Metabolic Inhibitors: A Comprehensive Treatise. New York: Academic Press
Ichas, F., Jouaville, L. S. & Mazat, J. P. (1997). Mitochondria are excitable organelles capable of generating and conveying electrical and calcium signals. Cell, 89, 1145–53
Jenkins, B. G., Rosas, H. D., Chen, Y. C.et al. (1998). 1H NMR spectroscopy studies of Huntington's disease: correlations with CAG repeat numbers. Neurology, 50, 1357–65
Kauppinen, R. A., Sihra, T. S. & Nicholls, D. G. (1987). Aminooxyacetic acid inhibits the malate–aspartate shuttle in isolated nerve terminals and prevents the mitochondria from using glycolytic substrates. Biochim. Biophys. Act., 930, 173–8
Kerr, J. F., Wyllie, A. H. & Currie, A. R. (1972). Apoptosis: a basic biological phenomenon with wide ranging implications in tissue kinetics. Br. J. Cance., 26, 239–47
Kiedrowski, L. & Costa, E. (1995). Glutamate-induced destabilization of intracellular calcium concentration homeostasis in cultured cerebellar granul cells: role of mitochondria in calcium buffering. Mol. Pharmacol., 53, 974–80
Kiedrowski, L., Brooker, G., Costa, E. & Wroblewski, J. T. (1994). Glutamate impairs neuronal calcium extrusion while reducing sodium gradient. Neuron, 12, 295–300
Kirkland, R. A., Windelborn, J. A., Kasprzak, J. M. & Franklin, J. L. (2002). A Bax-induced pro-oxidant state is critical for cytochrome c release during programmed neuronal death. J. Neurosci., 22, 6480–90
Koch, R. A. & Barrish, M. E. (1994). Perturbation of intracellular calcium and hydrogen ion regulation in cultured mouse hippocamp-al neurons by reduction of the sodium ion concentration gradient. J. Neurosci., 14, 2585–93
Kroemer, G. & Reed, J. C. (2000). Mitochondrial control of cell death. Nat. Med. 6, 513–19
Kuhl, D. E., Phelps, M. E., Markham, C. H., Metter, J., Riege, W. H. & Winter, J. (1982). Cerebral metabolism and atrophy in Huntington's disease determined by 18FDG and computed tomographic scan. Ann. Neurol., 12, 425–34
Leist, M., Single, B., Castoldi, A. F., Kuhnle, S. & Nicotera, P. (1997). Intracellular ATP concentration: a switch between apoptosis and necrosis. J. Exp. Med., 185, 1481–6
Li, L. Y., Luo, X. & Wang, X. (2001). Endonuclease G is an apoptotic DNase when released from mitochondria. Nature, 412, 95–9
Liu, X., Kim, C. N., Yang, J., Jemmerson, R. & Wang, X. (1996). Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell, 86, 147–57
Loschen, G., Azzi, A., Richter, C.et al. (1974). Superoxide radicals as precursors of mitochondrial hydrogen peroxide. FEBS Lett., 42, 68–72
Luo, X., Budihardjo, I., Zou, H., Slaughter, C. & Wang, X. (1998). Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell, 94, 481–90
Mata, M., Fink, D. J., Gainer, H.et al. (1980). Activity-dependent energy metabolism in rat posterior pituitary primarily reflects sodium pump activity. J. Neurochem., 34, 213–15
Matthews, R. T., Yang, L., Browne, S., Baik, M. & Beal, M. F. (1998a). Coenzyme Q10 administration increases brain mitochondrial ATP concentrations and exerts neuroprotective effects. Proc. Natl Acad. Sci., USA, 95, 8892–7
Matthews, R. T., Yang, L., Jenkins, B. G.et al. (1998b). Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington's disease. J. Neurosci., 18, 156–63
Mazziotta, J. C., Phelps, M. E. & Pahl, J. I. (1987). Reduced cerebral glucose metabolism in asymptomatic subjects at risk for Huntington's disease. N. Engl. J. Med., 316, 356–62
Murphy, A. N., Fiskum, G. & Beal, M. F. (1999). Mitochondria in neurodegeneration: bioenergetic function in cell life and death. J. Cereb. Blood Flow Metab., 19, 231–45
Narita, M., Shimizu, S., Ito, T.et al. (1998). Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria. Proc. Natl Acad. Sci., USA, 95, 14681–6
Nicklas, W. J., Vyas, I. & Heikkila, R. E. (1985). Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenyl-pyridine, a metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Life Sci., 36, 2503–8
Orth, M. & Schapira, A. H. V. (2001). Mitochondria and degenerative disorders. Am. J. Med. Genet. (Semin. Med. Genet.), 106, 27–36
Panov, A. V., Gutekunst, C- A., Leavitt, B. R.et al. (2002). Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines. Nat. Neurosci., 5, 731–6
Parker, W. D., Boyson, S. J. & Parks, J. K. (1989). Abnormalities of the electron transport chain in idiopathic Parkinson's disease. Ann. Neurol., 26, 719–23
Peng, T. I. & Greenamyre, J. T. (1998). Privileged access to mitochondria of calcium influx through N-methyl-D-aspartate receptors. Mol. Pharmacol., 53, 974–80
Pfeiffer, D. R., Gunter, T. E., Eliseev, R.et al. (2001). Release of Ca2+ from mitochondria via the saturable mechanisms and the permeability transition. IUBMB Life, 52, 205–12
Polyak, K., Xin, Y., Zweier, J. L., Kinzler, K. W. & Vogelstein, B. (1997). A model for p53-induced apoptosis. Nature, 289, 300–4
Pulsinelli, W. A. & Cooper, A. J. L. (1989). Metabolic encephalopathies and coma. In Basic Neurochemistry, ed. G. Siegel, B. Agranoff, R. W. Albers & P. Molinoff, pp. 765–81. New York: Raven Press
Puthalakath, H., Huang, D. C., O'Reilly, L. A., King, S. M. & Strasser, A. (1999). The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol. Cel., 3, 287–96
Raha, S. & Robinson, B. H. (2001). Mitochondria, oxygen free radicals, and apoptosis. Am. J. Med. Genet. (Semin. Med. Genet.), 106, 62–70
Ramsay, R. R., Krueger, M. J. & Youngster, S. K. (1991). Interaction of 1-methyl-4-phenylpyridinium ion (MPP+) and its analogs with the rotenone/piericidin binding site of NADH dehydrogenase. J. Neurochem., 56, 1184–90
Ravagnan, L., Roumier, T. & Kroemer, G. (2002). Mitochondria, the killer organells and their weapons. J. Cell Physiol., 192, 131–7
Schapira, A. H. V., Cooper, J. M., Dexter, D., Jenner, P., Clark, J. B. & Marsden, C. D. (1989). Mitochondrial complex I deficiency in Parkinson's disease. Lancet, i, 1269
Schapira, A. H. V., Mann, V. M. & Cooper, J. M. (1990). Anatomic and disease specificity of NADH CoQ1 reductase (complex I) deficiency in Parkinson's disease. J. Neurochem., 55, 2142–5
Schulz, J. B., Henshaw, D. R., Siwek, D.et al. (1995) Involvement of free radicals in excitotoxicity in vivo. J. Neurochem., 63, 2239–47
Sheehan, J. P., Swerdlow, R. H., Miller, S. W.et al. (1997a). Calcium homeostasis and reactive oxygen species production in cells transformed by mitochondria from individuals with sporadic Alzheimer's disease. J. Neurosci., 17, 4612–22
Sheehan, J. P., Swerdlow, R. H., Parker, W. D., Miller, S. W., Davis, R. E. & Tuttle, J. B. (1997b). Altered calcium homeostasis in cells transformed by mitochondria from individuals with Parkinson's disease. J. Neurochem., 68, 1221–33
Sherer, T. B., Betarbet, R., Stout, A. K.et al. (2002). An in vitro model of Parkinson's disease: linking mitochondrial impairment to altered alpha-synuclein metabolism and oxidative damage. J. Neurosci., 22, 7006–15
Shimizu, S., Narita, M . & Tsujimoto, Y. (1999). Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature, 399, 4833–7
Slater, E. C. (1973). The mechanism of action of the respiratory inhibitor, antimycin. Biochem. Biophys. Act., 301, 129–54
Stryer, L. (1988). In Biochemistry, pp. 349–426. New York: W. H. Freeman and Company
Stout, A. K., Raphael, H. M., Kanterewicz, B. I.et al. (1998). Glutamate-induced neuron death requires mitochondrial calcium uptake. Nat. Neurosci., 1, 366–73
Swerdlow, R. H., Parks, J. K., Cassarino, D. S.et al. (1997). Cybrids in Alzheimer's disease: a cellular model of the disease?Neurology, 49, 918–25
Swerdlow, R. H., Parks, J. K., Davis, J. N.et al. (1998). Matrilineal inheritance of complex I dysfunction I in a multigenerational Parkinson's disease family. Ann. Neurol., 44, 873–81
Tymianski, M., Charlton, M. P., Carlen, P. L. & Tator, C. H. (1993). Source specificity of early calcium neurotoxicity in cultured embryonic spinal neurons. J. Neurosci., 13, 2085–104
Vander Heiden, M. G., Chandel, N. S., Schumacker, P. T. & Thompson, C. B. (1999). Bcl-xl prevents cell death following growth factor withdrawal by facilitating mitochondrial ATP/ADP exchange. Mol. Cel., 3, 159–67
Verhagen, A. M., Silke, J., Ekert, P. G.et al. (2002). HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins. J. Biol. Chem., 277, 445–54
Volbracht, C., Leist, M. & Nicotera, P. (1999). ATP controls neuronal apoptosis triggered by microtubule breakdown or potassium deprivation. Mol. Med. 5, 477–89
Vogelstein, B., Lane, D. & Levine, A. J. (2000). Surfing the p53 network. Nature, 408, 307–10
Wieloch, T. (2001). Mitochondrial involvement in acute neurodegeneration. IUBMB Life, 52, 247–54
Woodfield, K., Ruck, A., Brdiczka, D. & Halestrap, A. P. (1998). Direct demonstration of a specific interaction between cyclophilin-D and the adenine nucleotide translocase confirms their role in the mitochondrial permeability transition. Biochem. J. 336, 287–90
Yan, L. J., Levine, R. L. & Sohal, R. S. (1997). Oxidative damage during aging targets mitochondrial aconitase. Proc. Natl Acad. Sci., USA, 94, 11168–72
Yue, T. L., Gou, J. L., Lysko, P. G., Cheng, H. Y., Barone, F. C. & Feuerstein, G. (1992). Neuroprotective effects of phenyl-t-butyl-nitrone in getbil global brain ischemia and in cultured rat cerebellar neurons. Brain Res., 574, 193–7
Zamzami, N., Susin, S. A., Marchetti, P.et al. (1996). Mitochondrial control of nuclear apoptosis. J. Exp. Med., 183, 1661–72
Zhang, Y., Marcillat, O., Giulivi, C., Ernster, L. & Davies, K. J. (1990). The oxidative inactivation of mitochondrial electron transport chain components and ATPase. J. Biol. Chem., 265, 16330–6
