Compromised respiratory adaptation and thermoregulation in aging and age-related diseases

Ageing Research Reviews - Tập 9 Số 1 - Trang 20-40 - 2010
Sic L. Chan1, Zelan Wei1, Srinivasulu Chigurupati1, Weihong Tu1
1Burnett School of Biomedical Sciences, College of Medicine, 4000 Central Florida Blvd, University of Central Florida, Orlando, FL 32816, United States.

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Abou-Sleiman, 2006, Expanding insights of mitochondrial dysfunction in Parkinson's disease, Nat. Rev. Neurosci., 7, 207, 10.1038/nrn1868

Aihara, 2001, The effects of cooling and rewarming on the neuronal activity of pyramidal neurons in guinea pig hippocampal slices, Brain Res., 893, 36, 10.1016/S0006-8993(00)03285-6

Amara, 2007, Mild mitochondrial uncoupling impacts cellular aging in human muscles in vivo, Proc. Natl. Acad. Sci. U.S.A., 104, 1057, 10.1073/pnas.0610131104

Andersson, 1995, Age-dependent modifications in the metabolism of mevalonate pathway lipids in rat brain, Mech. Ageing Dev., 3, 1, 10.1016/0047-6374(95)01642-2

Andrews, 2005, Mitochondrial uncoupling proteins in the CNS: in support of function and survival, Nat. Rev. Neurosci., 6, 829, 10.1038/nrn1767

Andrews, 2008, UCP2 mediates Ghrelin's action on NPY/AgRP neurons by lowering free radicals, Nature, 454, 846, 10.1038/nature07181

Andrews, 2006, Uncoupling protein-2 promotes nigrostriatal dopamine neuronal function, Eur. J. Neurosci., 24, 32, 10.1111/j.1460-9568.2006.04906.x

Andreyev, 1988, Carboxyatractylate inhibits the uncoupling effect of free fatty acids, FEBS Lett., 226, 265, 10.1016/0014-5793(88)81436-4

Andreyev, 1989, The ATP/ADP-antiporter is involved in the uncoupling effect of fatty acids on mitochondria, Eur. J. Biochem., 182, 585, 10.1111/j.1432-1033.1989.tb14867.x

Anello, 2005, Functional and morphological alterations of mitochondria in pancreatic beta cells from type 2 diabetic patients, Diabetologia, 48, 282, 10.1007/s00125-004-1627-9

Arsenijevic, 2000, Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production, Nat. Genet., 26, 435, 10.1038/82565

Asami, 2008, Effect of aging, caloric restriction, and uncoupling protein 3 (UCP3) on mitochondrial proton leak in mice, Exp. Gerontol., 43, 1069, 10.1016/j.exger.2008.09.010

Balaban, 2005, Mitochondria, oxidants, and aging, Cell, 120, 483, 10.1016/j.cell.2005.02.001

Barja, 1999, Mitochondrial oxygen radical generation and leak: sites of production in states 4 and 3, organ specificity, and relation to aging and longevity, J. Bioenerg. Biomembr., 31, 347, 10.1023/A:1005427919188

Barja, 2000, Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals, FASEB J., 14, 312, 10.1096/fasebj.14.2.312

Barros, 2004, Higher respiratory activity decreases mitochondrial reactive oxygen release and increases life span in Saccharomyces cerevisiae, J. Biol. Chem., 279, 49883, 10.1074/jbc.M408918200

Bartke, 2004, Life extension in the dwarf mouse, Curr. Top. Dev. Biol., 63, 189, 10.1016/S0070-2153(04)63006-7

Bartke, 2001, Extending the lifespan of long-lived mice, Nature, 414, 412, 10.1038/35106646

Bates, 2003, Huntingtin aggregation and toxicity in Huntington's disease, Lancet, 361, 1642, 10.1016/S0140-6736(03)13304-1

Bayne, 2005, Enhanced catabolism of mitochondrial superoxide/hydrogen peroxide and aging in transgenic Drosophila, Biochem. J., 391, 277, 10.1042/BJ20041872

Beal, 2005, Mitochondria take center stage in aging and neurodegeneration, Ann. Neurol., 58, 495, 10.1002/ana.20624

Bechmann, 2002, Brain mitochondrial uncoupling protein 2 (UCP2): a protective stress signal in neuronal injury, Biochem. Pharmacol., 64, 363, 10.1016/S0006-2952(02)01166-8

Bernal-Mizrachi, 2002, Respiratory uncoupling lowers blood pressure through a leptin-dependent mechanism in genetically obese mice, Arterioscler. Thromb. Vasc. Biol., 22, 961, 10.1161/01.ATV.0000019404.65403.71

Bevilacqua, 2004, Effects of short- and medium-term calorie restriction on muscle mitochondrial proton leak and reactive oxygen species production, Am. J. Physiol. Endocrinol. Metab., 286, E852, 10.1152/ajpendo.00367.2003

Bevilacqua, 2005, Long-term caloric restriction increases UCP3 content but decreases proton leak and reactive oxygen species production in rat skeletal muscle mitochondria, Am. J. Physiol. Endocrinol. Metab., 289, E429, 10.1152/ajpendo.00435.2004

Bishop, 2007, Genetic links between diet and lifespan: shared mechanisms from yeast to humans, Nat. Rev. Genet., 8, 835, 10.1038/nrg2188

Blanc, 2003, Protective role of uncoupling protein 2 in atherosclerosis, Circulation, 107, 388, 10.1161/01.CIR.0000051722.66074.60

Blümcke, 1999, An increase of hippocampal calretinin-immunoreactive neurons correlates with early febrile seizures in temporal lobe epilepsy, Acta Neuropathol., 97, 31, 10.1007/s004010050952

Boffoli, 1994, Decline with age of the respiratory chain activity in human skeletal muscle, Biochim. Biophys. Acta, 1226, 73, 10.1016/0925-4439(94)90061-2

Boillée, 2006, ALS: a disease of motor neurons and their nonneuronal neighbors, Neuron, 52, 39, 10.1016/j.neuron.2006.09.018

Bonawitz, 2007, Reduced TOR signaling extends chronological life span via increased respiration and upregulation of mitochondrial gene expression, Cell Metab., 5, 265, 10.1016/j.cmet.2007.02.009

Bordone, 2006, Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta cells, PLoS Biol., 4, e295, 10.1371/journal.pbio.0040295

Bouillaud, 2001, Homologues of the uncoupling protein from brown adipose tissue (UCP1): UCP2, UCP3, BMCP1 and UCP4, Biochim. Biophys. Acta, 1504, 107, 10.1016/S0005-2728(00)00241-3

Boveris, 1973, The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen, Biochem. J., 134, 707, 10.1042/bj1340707

Bowling, 1993, Superoxide dismutase activity, oxidative damage, and mitochondrial energy metabolism in familial and sporadic amyotrophic lateral sclerosis, J. Neurochem., 61, 2322, 10.1111/j.1471-4159.1993.tb07478.x

Brand, 1977, The stoicheiometric relationships between electron transport, proton translocation and adenosine triphosphate synthesis and hydrolysis in mitochondria, Biochem. Soc. Trans, 5, 1615, 10.1042/bst0051615

Brand, 1990, The proton leak across the mitochondrial inner membrane, Biochim. Biophys. Acta, 1018, 128, 10.1016/0005-2728(90)90232-S

Brand, 2000, Uncoupling to survive? The role of mitochondrial inefficiency in ageing, Exp. Gerontol., 35, 811, 10.1016/S0531-5565(00)00135-2

Brand, 2004, Mitochondrial superoxide and aging: uncoupling-protein activity and superoxide production, Biochem. Soc. Symp., 71, 203, 10.1042/bss0710203

Brand, 1991, Evolution of energy metabolism. Proton permeability of the inner membrane of liver mitochondria is greater in a mammal than in a reptile, Biochem. J., 275, 81, 10.1042/bj2750081

Brand, 2005, Physiological functions of the mitochondrial uncoupling proteins UCP2 and UCP3, Cell Metab., 2, 85, 10.1016/j.cmet.2005.06.002

Brand, 2005, The basal proton conductance of mitochondria depends on adenine nucleotide translocase content, Biochem. J., 392, 353, 10.1042/BJ20050890

Brand, 2002, Oxidative damage and phospholipid fatty acyl composition in skeletal muscle mitochondria from mice underexpressing or overexpressing uncoupling protein 3, Biochem. J., 368, 597, 10.1042/bj20021077

Brookes, 2005, Mitochondrial H(+) leak and ROS generation: an odd couple, Free Radic. Biol. Med., 38, 12, 10.1016/j.freeradbiomed.2004.10.016

Brookes, 1998, The proton permeability of the inner membrane of liver mitochondria from ectothermic and endothermic vertebrates and from obese rats: correlations with standard metabolic rate and phospholipid fatty acid composition, Comp. Biochem. Physiol. B: Biochem. Mol. Biol., 119, 325, 10.1016/S0305-0491(97)00357-X

Brouillet, 2005, 3-Nitropropionic acid: a mitochondrial toxin to uncover physiopathological mechanisms underlying striatal degeneration in Huntington's disease, J. Neurochem., 95, 1521, 10.1111/j.1471-4159.2005.03515.x

Brown, 1990, Control of respiration and oxidative phosphorylation in isolated rat liver cells, Eur. J. Biochem., 192, 355, 10.1111/j.1432-1033.1990.tb19234.x

Brown, 2002, Glucose induces and leptin decreases expression of uncoupling protein-2 mRNA in human islets, FEBS Lett., 513, 189, 10.1016/S0014-5793(02)02296-2

Browne, 2004, The energetics of Huntington's disease, Neurochem. Res., 29, 531, 10.1023/B:NERE.0000014824.04728.dd

Browne, 1997, Oxidative damage and metabolic dysfunction in Huntington's disease: selective vulnerability of the basal ganglia, Ann. Neurol., 41, 646, 10.1002/ana.410410514

Bruijn, 2004, Annu. Rev. Neurosci., 27, 723, 10.1146/annurev.neuro.27.070203.144244

Brustovetsky, 1994, The reconstituted ADP/ATP carrier can mediate H+ transport by free fatty acids, which is further stimulated by mersalyl, J. Biol. Chem., 269, 27329, 10.1016/S0021-9258(18)46989-X

Cadenas, 1999, UCP2 and UCP3 rise in starved rat skeletal muscle but mitochondrial proton conductance is unchanged, FEBS Lett., 462, 257, 10.1016/S0014-5793(99)01540-9

Cadenas, 2000, AMP decreases the efficiency of skeletal-muscle mitochondria, Biochem. J., 351, 307, 10.1042/0264-6021:3510307

Cadenas, 2002, The basal proton conductance of skeletal muscle mitochondria from transgenic mice overexpressing or lacking uncoupling protein-3, J. Biol. Chem., 277, 2773, 10.1074/jbc.M109736200

Cairns, 1998, Mitochondrial oxidative phosphorylation thermodynamic efficiencies reflect physiological organ roles, Am. J. Physiol., 274, 1376

Caldeira da Silva, 2008, Mild mitochondrial uncoupling in mice affects energy metabolism, redox balance and longevity, Aging Cell, 7, 552, 10.1111/j.1474-9726.2008.00407.x

Cannon, 2004, Brown adipose tissue: function and physiological significance, Physiol. Rev., 84, 277, 10.1152/physrev.00015.2003

Cannon, 2006, Uncoupling proteins: a role in protection against reactive oxygen species—or not?, Biochim. Biophys. Acta, 1757, 449, 10.1016/j.bbabio.2006.05.016

Chan, 2001, Increased uncoupling protein-2 levels in β-cells are associated with impaired glucose-stimulated insulin secretion: mechanism of action, Diabetes, 50, 1302, 10.2337/diabetes.50.6.1302

Chan, 2006, Mitochondrial uncoupling protein-4 regulates calcium homeostasis and sensitivity to store depletion-induced apoptosis in neural cells, J. Biol. Chem., 281, 37391, 10.1074/jbc.M605552200

Cheney, 1983, The effect of dietary restriction of varying duration on survival, tumor patterns, immune function, and body temperature in B10C3F1 female mice, J. Gerontol., 38, 420, 10.1093/geronj/38.4.420

Clancy, 2001, Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein, Science, 292, 104, 10.1126/science.1057991

Clapham, 2000, Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean, Nature, 406, 415, 10.1038/35019082

Cleveland, 2000, Oxidation versus aggregation—how do SOD1 mutants cause ALS?, Nat. Med., 6, 1320, 10.1038/82122

Conley, 2007, Mitochondrial dysfunction: impact on exercise performance and cellular aging, Exerc. Sport Sci. Rev., 35, 43, 10.1249/JES.0b013e31803e88e9

Conti, 2006, Transgenic mice with a reduced core body temperature have an increased life span, Science, 314, 825, 10.1126/science.1132191

Conti, 2005, Uncoupling protein 2 protects dopaminergic neurons from acute 1, 2, 3, 6-methyl-phenyl-tetrahydropyridine toxicity, J. Neurochem., 93, 493, 10.1111/j.1471-4159.2005.03052.x

Cui, 2006, Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration, Cell, 127, 59, 10.1016/j.cell.2006.09.015

Cutler, 2002, Evidence that accumulation of ceramides and cholesterol esters mediates oxidative stress-induced death of motor neurons in amyotrophic lateral sclerosis, Ann. Neurol., 52, 448, 10.1002/ana.10312

Davies, 1997, Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation, Cell, 90, 537, 10.1016/S0092-8674(00)80513-9

Dawson, 2003, Molecular pathways of neurodegeneration in Parkinson's disease, Science, 302, 819, 10.1126/science.1087753

De Felice, 2004, Targeting the neurotoxic species in Alzheimer's disease: inhibitors of Abeta oligomerization, FASEB J., 18, 1366, 10.1096/fj.04-1764com

de la Monte, 2006, Molecular indices of oxidative stress and mitochondrial dysfunction occur early and often progress with severity of Alzheimer's disease, J. Alzheimers Dis., 9, 167, 10.3233/JAD-2006-9209

Deierborg, 2008, Overexpression of UCP2 protects thalamic neurons following global ischemia in the mouse, J. Cereb. Blood Flow Metab., 28, 1186, 10.1038/jcbfm.2008.8

Derdak, 2008, The mitochondrial uncoupling protein-2 promotes chemoresistance in cancer cells, Cancer Res., 68, 2813, 10.1158/0008-5472.CAN-08-0053

Derouillet, 2005, 3-Nitropropionic acid: a mitochondrial toxin to uncover physiopathological mechanisms underlying striatal degeneration in Huntington's disease, J. Neurochem., 95, 1521, 10.1111/j.1471-4159.2005.03515.x

Desquiret, 2006, Dinitrophenol-induced mitochondrial uncoupling in vivo triggers respiratory adaptation in HepG2 cells, Biochim. Biophys. Acta, 1757, 21, 10.1016/j.bbabio.2005.11.005

Dhahbi, 2001, Caloric restriction alters the feeding response of key metabolic enzyme genes, Mech. Ageing Dev., 122, 1033, 10.1016/S0047-6374(01)00230-5

Dhaliwal, 2000, Mitochondrial DNA deletion mutation levels are elevated in ALS brains, Neuroreport, 11, 2507, 10.1097/00001756-200008030-00032

Diano, 2003, Uncoupling protein 2 prevents neuronal death including that occurring during seizures: a mechanism for preconditioning, Endocrinology, 144, 5014, 10.1210/en.2003-0667

Dirks, 2006, Mitochondrial DNA mutations, energy metabolism and apoptosis in aging muscle, Ageing Res. Rev., 5, 179, 10.1016/j.arr.2006.03.002

Doerner, 1997, Tissue-specific transcription pattern of the adenine nucleotide translocase isoforms in humans, FEBS Lett., 414, 258, 10.1016/S0014-5793(97)01000-4

Dumas, 2004, Food restriction affects energy metabolism in rat liver mitochondria, Biochim. Biophys. Acta, 1670, 126, 10.1016/j.bbagen.2003.11.002

Dunah, 2002, Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease, Science, 296, 2238, 10.1126/science.1072613

Dupuis, 2003, Up-regulation of mitochondrial uncoupling protein 3 reveals an early muscular metabolic defect in amyotrophic lateral sclerosis, FASEB J., 17, 2091, 10.1096/fj.02-1182fje

Dupuis, 2009, Muscle mitochondrial uncoupling dismantles neuromuscular junction and triggers distal degeneration of motor neurons, PLoS ONE, 4, e5390, 10.1371/journal.pone.0005390

Echtay, 2007, Mitochondrial uncoupling proteins—what is their physiological role?, Free Radic. Biol. Med., 43, 1351, 10.1016/j.freeradbiomed.2007.08.011

Echtay, 2003, A signalling role for 4-hydroxy-2-nonenal in regulation of mitochondrial uncoupling, EMBO J., 22, 4103, 10.1093/emboj/cdg412

Echtay, 2002, Superoxide activates mitochondrial uncoupling proteins, Nature, 415, 96, 10.1038/415096a

Enerback, 1997, Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese, Nature, 387, 90, 10.1038/387090a0

Esteves, 2005, The reactions catalysed by the mitochondrial uncoupling proteins UCP2 and UCP3, Biochim. Biophys. Acta, 1709, 35, 10.1016/j.bbabio.2005.06.002

Evans, 2008, Mitochondrial uncoupling protein-2 mediates steatotic liver injury following ischemia/reperfusion, J. Biol. Chem., 283, 8573, 10.1074/jbc.M706784200

Facundo, 2005, Mitochondrial ATP-sensitive K+ channels prevent oxidative stress, permeability transition and cell death, J. Bioenerg. Biomembr., 37, 75, 10.1007/s10863-005-4130-1

Ferranti, 2003, Mitochondrial ATP-sensitive K+ channel opening decreases reactive oxygen species generation, FEBS Lett., 536, 51, 10.1016/S0014-5793(03)00007-3

Ferri, 2005, Global prevalence of dementia: a Delphi consensus study, Lancet, 366, 2112, 10.1016/S0140-6736(05)67889-0

Fridell, 2005, Targeted expression of the human uncoupling protein 2 (hUCP2) to adult neurons extends life span in the fly, Cell Metab., 1, 145, 10.1016/j.cmet.2005.01.005

Gable, 2006, Variation in the UCP2–UCP3 gene cluster predicts the development of type 2 diabetes in healthy middle-aged men, Diabetes, 55, 1504, 10.2337/db05-1645

García-Martinez, 2001, Overexpression of UCP3 in cultured human muscle lowers mitochondrial membrane potential, raises ATP/ADP ratio, and favors fatty acid vs. glucose oxidation, FASEB J., 15, 2033, 10.1096/fj.00-0828fje

Gárdián, 2004, Huntington's disease: pathomechanism and therapeutic perspectives, J. Neural Transm., 111, 1485, 10.1007/s00702-004-0201-4

Garlid, 2003, Mitochondrial potassium transport: the K(+) cycle, Biochim. Biophys. Acta, 1606, 23, 10.1016/S0005-2728(03)00108-7

Gates, 2007, Respiratory uncoupling in skeletal muscle delays death and diminishes age-related disease, Cell Metab., 6, 497, 10.1016/j.cmet.2007.10.010

Gong, 2000, Lack of obesity and normal response to fasting and thyroid hormone in mice lacking uncoupling protein-3, J. Biol. Chem., 275, 16251, 10.1074/jbc.M910177199

Gonzales-Pacheco, 1993, Energy restriction reduces metabolic rate in adult male Fisher-344 rats, J. Nutr., 123, 90, 10.1093/jn/123.1.90

Gredilla, 2001, Caloric restriction decreases mitochondrial free radical generation at complex I and lowers oxidative damage to mitochondrial DNA in the rat heart, FASEB J., 15, 1589, 10.1096/fj.00-0764fje

Gu, 1996, Mitochondrial defect in Huntington's disease caudate nucleus, Ann. Neurol., 39, 385, 10.1002/ana.410390317

Guarente, 2008, Mitochondria—a nexus for aging, calorie restriction, and sirtuins?, Cell, 132, 171, 10.1016/j.cell.2008.01.007

Guarente, 2005, Calorie restriction—the SIR2 connection, Cell, 120, 473, 10.1016/j.cell.2005.01.029

Hafner, 1988, Altered relationship between protonmotive force and respiration rate in non-phosphorylating liver mitochondria isolated from rats of different thyroid hormone status, Eur. J. Biochem., 178, 511, 10.1111/j.1432-1033.1988.tb14477.x

Hagopian, 2005, Long-term calorie restriction reduces proton leak and hydrogen peroxide production in liver mitochondria, Am. J. Physiol. Endocrinol. Metab., 288, E674, 10.1152/ajpendo.00382.2004

Hajieva, 2006, Antioxidants as a potential therapy against age-related neurodegenerative diseases: amyloid Beta toxicity and Alzheimer's disease, Curr. Pharm. Des., 12, 699, 10.2174/138161206775474297

Hansford, 1997, Dependence of H2O2 formation by rat heart mitochondria on substrate availability and donor age, J. Bioenerg. Biomembr., 29, 89, 10.1023/A:1022420007908

Harman, 1956, Aging: a theory based on free radical and radiation chemistry, J. Gerontol., 11, 298, 10.1093/geronj/11.3.298

Harper, 2001, Mitochondrial uncoupling as a target for drug development for the treatment of obesity, Obes. Rev., 2, 255, 10.1046/j.1467-789X.2001.00043.x

Harper, 2002, Artifactual uncoupling by uncoupling protein 3 in yeast mitochondria at the concentrations found in mouse and rat skeletal-muscle mitochondria, Biochem. J., 361, 49, 10.1042/0264-6021:3610049

Harper, 2002, Characterization of a novel metabolic strategy used by drug-resistant tumor cells, FASEB J., 16, 1550, 10.1096/fj.02-0541com

Harper, 1998, Age-related increase in mitochondrial proton leak and decrease in ATP turnover reactions in mouse hepatocytes, Am. J. Physiol., 275, 197

Hashimoto, 1999, Oxidative stress induces amyloid-like aggregate formation of NACP/alpha-synuclein in vitro, Neuroreport, 10, 717, 10.1097/00001756-199903170-00011

Hashimoto, 2003, Role of protein aggregation in mitochondrial dysfunction and neurodegeneration in Alzheimer's and Parkinson's diseases, Neuromol. Med., 4, 21, 10.1385/NMM:4:1-2:21

Hekimi, 2003, Genetics and the specificity of the aging process, Science, 299, 1351, 10.1126/science.1082358

Higami, 2004, Adipose tissue energy metabolism: altered gene expression profile of mice subjected to long-term caloric restriction, FASEB J., 18, 415, 10.1096/fj.03-0678fje

Himms-Hagen, 2001, Physiological role of UCP3 may be export of fatty acids from mitochondria when fatty acid oxidation predominates: an hypothesis, Exp. Biol. Med. (Maywood), 226, 78, 10.1177/153537020122600204

Himms-Hagen, 1989, Brown adipose tissue thermogenesis and obesity, Prog. Lipid Res., 28, 67, 10.1016/0163-7827(89)90009-X

Hoch, 1992, Cardiolipins and biomembrane function, Biochim. Biophys. Acta, 1113, 71, 10.1016/0304-4157(92)90035-9

Horimoto, 2004, Uncoupling protein-2 deficiency promotes oxidant stress and delays liver regeneration in mice, Hepatology, 39, 386, 10.1002/hep.20047

Horimoto, 2004, Expression of uncoupling protein-2 in human colon cancer, Clin. Cancer Res., 10, 6203, 10.1158/1078-0432.CCR-04-0419

Horrum, 1990, Thyroid harmone effects on the proton permeability of rat liver mitochondria, Mol. Cell Endocrinol., 68, 137, 10.1016/0303-7207(90)90186-C

Horvath, 2003, Mitochondrial uncoupling protein 2 in the central nervous system: neuromodulator and neuroprotector, Biochem. Pharmacol., 65, 1917, 10.1016/S0006-2952(03)00143-6

Hulbert, 1999, Membranes as possible pacemakers of metabolism, J. Theor. Biol., 199, 257, 10.1006/jtbi.1999.0955

Hunter, 1999, Low body temperature in long-lived Ames dwarf mice at rest and during stress, Physiol. Behav., 67, 433, 10.1016/S0031-9384(99)00098-0

Huntington's Disease Collaborative Research Group, 1993, A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes, Cell, 72, 971, 10.1016/0092-8674(93)90585-E

Hurlbert, 1999, Mice transgenic for an expanded CAG repeat in the Huntington's disease gene develop diabetes, Diabetes, 48, 649, 10.2337/diabetes.48.3.649

Ingram, 2006, Calorie restriction mimetics: an emerging research field, Aging Cell, 5, 97, 10.1111/j.1474-9726.2006.00202.x

Jezek, 2002, Possible physiological roles of mitochondrial uncoupling proteins—UCPn, Int. J. Biochem. Cell Biol., 34, 1190, 10.1016/S1357-2725(02)00061-4

Jin, 2004, The mitochondrial uncoupling agent 2,4-dinitrophenol improves mitochondrial function, attenuates oxidative damage, and increases white matter sparing in the contused spinal cord, J. Neurotrauma, 21, 1396, 10.1089/neu.2004.21.1396

Johnson-Cadwell, 2007, ‘Mild Uncoupling’ does not decrease mitochondrial superoxide levels in cultured cerebellar granule neurons but decreases spare respiratory capacity and increases toxicity to glutamate and oxidative stress, J. Neurochem., 101, 1619, 10.1111/j.1471-4159.2007.04516.x

Kaeberlein, 1999, The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms, Genes Dev., 13, 2570, 10.1101/gad.13.19.2570

Keller, 1998, Roles of lipid peroxidation in modulation of cellular signaling pathways, cell dysfunction, and death in the nervous system, Rev. Neurosci., 9, 105, 10.1515/REVNEURO.1998.9.2.105

Kerner, 2001, Aging skeletal muscle mitochondria in the rat: decreased uncoupling protein-3 content, Am. J. Physiol. Endocrinol. Metab., 281, 1054, 10.1152/ajpendo.2001.281.5.E1054

Kim-Han, 2005, Mitochondrial uncoupling proteins in the central nervous system, Antioxid. Redox Signal., 7, 1173, 10.1089/ars.2005.7.1173

Klingenberg, 1993, Dialectics in carrier research: the ADP/ATP carrier and the uncoupling protein, J. Bioenerg. Biomembr., 25, 447, 10.1007/BF01108402

Klingenberg, 2008, The ADP and ATP transport in mitochondria and its carrier, Biochim. Biophys. Acta, 1778, 1978, 10.1016/j.bbamem.2008.04.011

Kong, 1998, Massive mitochondrial degeneration in motor neurons triggers the onset of amyotrophic lateral sclerosis in mice expressing a mutant SOD1, J. Neurosci., 18, 324132, 10.1523/JNEUROSCI.18-09-03241.1998

Korde, 2005, The mitochondrial uncoupler 2,4-dinitrophenol attenuates tissue damage and improves mitochondrial homeostasis following transient focal cerebral ischemia, J. Neurochem., 94, 1676, 10.1111/j.1471-4159.2005.03328.x

Korshunov, 1997, High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria, FEBS Lett., 416, 15, 10.1016/S0014-5793(97)01159-9

Kowaltowski, 1998, Activation of the potato plant uncoupling mitochondrial protein inhibits reactive oxygen species generation by the respiratory chain, FEBS Lett., 425, 213, 10.1016/S0014-5793(98)00231-2

Krause, 2004, Supramolecular organization of cytochrome c oxidase- and alternative oxidase-dependent respiratory chains in the filamentous fungus Podospora anserina, J. Biol. Chem., 279, 26453, 10.1074/jbc.M402756200

Krauss, 2003, Superoxide-mediated activation of uncoupling protein 2 causes pancreatic beta cell dysfunction, J. Clin. Invest., 112, 1831, 10.1172/JCI200319774

Kristián, 1998, Calcium in ischemic cell death, Stroke, 29, 705, 10.1161/01.STR.29.3.705

Ku, 1993, Relationship between mitochondrial superoxide and hydrogen peroxide production and longevity of mammalian species, Free Radic. Biol. Med., 15, 621, 10.1016/0891-5849(93)90165-Q

Laganiere, 1993, Modulation of membrane phospholipid fatty acid composition by age and food restriction, Gerontology, 39, 7, 10.1159/000213509

Lal, 2001, Effects of caloric restriction on skeletal muscle mitochondrial proton leak in aging rats, J. Gerontol. A: Biol. Sci. Med. Sci., 56, B116, 10.1093/gerona/56.3.B116

Lambert, 2004, Inhibitors of the quinone-binding site allow rapid superoxide production from mitochondrial NADH:ubiquinone oxidoreductase (complex I), J. Biol. Chem., 279, 39414, 10.1074/jbc.M406576200

Lambert, 2005, Lack of effect of caloric restriction on bioenergetics and reactive oxygen species production in intact rat hepatocytes, J. Gerontol. A: Biol. Sci. Med. Sci., 60, 175, 10.1093/gerona/60.2.175

Lambert, 2004, Exogenous insulin can reverse the effects of caloric restriction on mitochondria, Biochem. Biophys. Res. Commun., 316, 1196, 10.1016/j.bbrc.2004.03.005

Lambert, 2004, The effect of aging and caloric restriction on mitochondrial protein density and oxygen consumption, Exp. Gerontol., 39, 289, 10.1016/j.exger.2003.12.009

Langston, 1984, 1-Methyl-4-phenylpyridinium ion (MPP+): identification of a metabolite of MPTP, a toxin selective to the substantia nigra, Neurosci. Lett., 48, 87, 10.1016/0304-3940(84)90293-3

Larsen, 2005, Nuclear and mitochondrial DNA repair: similar pathways?, Mitochondrion, 5, 89, 10.1016/j.mito.2005.02.002

Lee, 2002, Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts, Proc. Natl. Acad. Sci. U.S.A., 99, 14988, 10.1073/pnas.232308999

Lee, 2002, Formation and removal of alpha-synuclein aggregates in cells exposed to mitochondrial inhibitors, J. Biol. Chem., 277, 5411, 10.1074/jbc.M105326200

Li, 2000, Hyperglycemia enhances extracellular glutamate accumulation in rats subjected to forebrain ischemia, Stroke, 31, 183, 10.1161/01.STR.31.1.183

Li, 2008, UCP-2 and UCP-3 proteins are differentially regulated in pancreatic beta-cells, PLoS ONE, 3, e1397, 10.1371/journal.pone.0001397

Liss, 2005, K-ATP channels promote the differential degeneration of dopaminergic midbrain neurons, Nat Neurosci., 8, 1742, 10.1038/nn1570

Liu, 2006, Mitochondrial UCP4 mediates an adaptive shift in energy metabolism and increases the resistance of neurons to metabolic and oxidative stress, Neuromol. Med., 8, 389, 10.1385/NMM:8:3:389

López-Lluch, 2006, Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency, Proc. Natl. Acad. Sci. U.S.A., 103, 1768, 10.1073/pnas.0510452103

Lowell, 2000, Towards a molecular understanding of adaptive thermogenesis, Nature, 404, 652, 10.1038/35007527

MacLellan, 2005, Physiological increases in uncoupling protein 3 augment fatty acid oxidation and decrease reactive oxygen species production without uncoupling respiration in muscle cells, Diabetes, 54, 2343, 10.2337/diabetes.54.8.2343

Mao, 1999, UCP4, a novel brain-specific mitochondrial protein that reduces membrane potential in mammalian cells, FEBS Lett., 443, 326, 10.1016/S0014-5793(98)01713-X

Maragos, 2003, Pre- or post-treatment with the mitochondrial uncoupler 2,4-dinitrophenol attenuates striatal quinolinate lesions, Brain Res., 966, 312, 10.1016/S0006-8993(02)04225-7

Marcinek, 2005, Reduced mitochondrial coupling in vivo alters cellular energetics in aged mouse skeletal muscle, J. Physiol., 569, 467, 10.1113/jphysiol.2005.097782

Mattiasson, 2003, Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma, Nat. Med., 9, 1062, 10.1038/nm903

Mattson, 2004, Pathways towards and away from Alzheimer's disease, Nature, 430, 631, 10.1038/nature02621

Mattson, 2003, Meal size and frequency affect neuronal plasticity and vulnerability to disease: cellular and molecular mechanisms, J. Neurochem., 84, 417, 10.1046/j.1471-4159.2003.01586.x

Mattson, 2001, Suppression of brain aging and neurodegenerative disorders by dietary restriction and environmental enrichment: molecular mechanisms, Mech. Ageing, 122, 757, 10.1016/S0047-6374(01)00226-3

Mattson, 2008, Mitochondria in neuroplasticity and neurological disorders, Neuron, 60, 748, 10.1016/j.neuron.2008.10.010

Mattson, 2002, Energetics and oxidative stress in synaptic plasticity and neurodegenerative disorders, Neuromol. Med., 2, 215, 10.1385/NMM:2:2:215

Mattson, 2003, Mitochondrial potassium channels and uncoupling proteins in synaptic plasticity and neuronal cell death, Biochem. Biophys. Res. Commun., 304, 539, 10.1016/S0006-291X(03)00627-2

McCay, 1989, The effect of retarded growth upon the length of life span and upon the ultimate body size. 1935, Nutrition, 5, 155

Merry, 2004, Oxidative stress and mitochondrial function with aging—the effects of calorie restriction, Aging Cell, 3, 7, 10.1046/j.1474-9728.2003.00074.x

Michikawa, 1999, Aging-dependent large accumulation of point mutations in the human mtDNA control region for replication, Science, 286, 774, 10.1126/science.286.5440.774

Milakovic, 2005, Mitochondrial respiration and ATP production are significantly impaired in striatal cells expressing mutant huntingtin, J. Biol. Chem., 280, 30773, 10.1074/jbc.M504749200

Millet, 1997, Increased uncoupling protein-2 and -3 mRNA expression during fasting in obese and lean humans, J. Clin. Invest., 100, 2665, 10.1172/JCI119811

Minamiyama, 2007, Calorie restriction improves cardiovascular risk factors via reduction of mitochondrial reactive oxygen species in type II diabetic rats, J. Pharmacol. Exp. Ther., 320, 535, 10.1124/jpet.106.110460

Miwa, 2003, Mitochondrial matrix reactive oxygen species production is very sensitive to mild uncoupling, Biochem. Soc. Trans., 31, 1300, 10.1042/bst0311300

Miwa, 2004, Lack of correlation between mitochondrial reactive oxygen species production and life span in Drosophila, Ann. N.Y. Acad. Sci., 1019, 388, 10.1196/annals.1297.069

Mizuno, 2000, Distinct regulation of brain mitochondrial carrier protein-1 and uncoupling protein-2 genes in the rat brain during cold exposure and aging, Biochem. Biophys. Res. Commun., 278, 691, 10.1006/bbrc.2000.3859

Moore, 2005, Molecular pathophysiology of Parkinson's disease, Annu. Rev. Neurosci., 28, 57, 10.1146/annurev.neuro.28.061604.135718

Nakase, 2007, Amplified expression of uncoupling proteins in human brain ischemic lesions, Neuropathology, 27, 442, 10.1111/j.1440-1789.2007.00815.x

Navarro, 2004, Rat brain and liver mitochondria develop oxidative stress and lose enzymatic activities on aging, Am. J. Physiol. Regul. Integr. Comp. Physiol., 287, 1244, 10.1152/ajpregu.00226.2004

Nedergaard, 2003, The ‘novel’ ‘uncoupling’ proteins UCP2 and UCP3: what do they really do? Pros and cons for suggested functions, Exp. Physiol., 88, 65, 10.1113/eph8802502

Nègre-Salvayre, 1997, A role for uncoupling protein-2 as a regulator of mitochondrial hydrogen peroxide generation, FASEB J., 11, 809, 10.1096/fasebj.11.10.9271366

Nicholls, 1998, Mitochondria and neuronal glutamate excitotoxicity, Biochim. Biophys. Acta, 1366, 97, 10.1016/S0005-2728(98)00123-6

Nicholls, 1976, Hamster brown-adipose-tissue mitochondria Purine nucleotide control of the ion conductance of the inner membrane, the nature of the nucleotide binding site, Eur. J. Biochem., 62, 223, 10.1111/j.1432-1033.1976.tb10151.x

Nobes, 1989, The contribution of ATP turnover by the Na+/K+-ATPase to the rate of respiration of hepatocytes. Effects of thyroid status and fatty acids, Biochim. Biophys. Acta, 976, 241, 10.1016/S0005-2728(89)80236-1

Nunomura, 2006, Involvement of oxidative stress in Alzheimer disease, J. Neuropathol. Exp. Neurol., 65, 631, 10.1097/01.jnen.0000228136.58062.bf

Orr, 1994, Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster, Science, 263, 1128, 10.1126/science.8108730

Padalko, 2005, Uncoupler of oxidative phosphorylation prolongs the lifespan of Drosophila, Biochemistry (Mosc.), 70, 986, 10.1007/s10541-005-0213-1

Pamplona, 2000, Low fatty acid unsaturation: a mechanism for lowered lipoperoxidative modification of tissue proteins in mammalian species with long life spans, J. Gerontol. A: Biol. Sci. Med. Sci., 55, B286, 10.1093/gerona/55.6.B286

Pamplona, 2002, Membrane fatty acid unsaturation, protection against oxidative stress, and maximum life span: a homeoviscous-longevity adaptation?, Ann. N.Y. Acad. Sci., 959, 475, 10.1111/j.1749-6632.2002.tb02118.x

Pamplona, 2002, Oxidative, glycoxidative and lipoxidative damage to rat heart mitochondrial proteins is lower after 4 months of caloric restriction than in age-matched controls, Mech. Ageing Dev., 123, 1437, 10.1016/S0047-6374(02)00076-3

Paolisso, 1996, Glucose tolerance and insulin action in healthy centenarians, Am. J. Physiol., 270, 890

Parascandola, 1974, Dinitrophenol and bioenergetics: an historical perspective, Mol. Cell. Biochem., 5, 69, 10.1007/BF01874175

Pasinelli, 2006, Molecular biology of amyotrophic lateral sclerosis: insights from genetics, Nat. Rev. Neurosci., 7, 710, 10.1038/nrn1971

Patel, 2003, Age-related changes in neuronal glucose uptake in response to glutamate and beta-amyloid, J. Neurosci. Res., 72, 527, 10.1002/jnr.10602

Pecqueur, 2001, Uncoupling protein 2, in vivo distribution, induction upon oxidative stress, and evidence for translational regulation, J. Biol. Chem., 276, 8705, 10.1074/jbc.M006938200

Pecqueur, 2001, Genetic and physiological analysis of the role of uncoupling proteins in human energy homeostasis, J. Mol. Med., 79, 48, 10.1007/s001090000150

Pedersen, 2000, Regulation of uncoupling protein (UCP) 2 and 3 in adipose and muscle tissue by fasting and growth hormone treatment in obese humans, Int. J. Obes. Relat. Metab. Disord., 24, 968, 10.1038/sj.ijo.0801265

Pedersen, 1999, No benefit of dietary restriction on disease onset or progression in amyotrophic lateral sclerosis Cu/Zn-superoxide dismutase mutant mice, Brain Res., 833, 117, 10.1016/S0006-8993(99)01471-7

Pisani, 2006, Enhanced sensitivity of DJ-1-deficient dopaminergic neurons to energy metabolism impairment: role of Na+/K+ ATPase, Neurobiol. Dis., 23, 54, 10.1016/j.nbd.2006.02.001

Porter, 1995, Causes of differences in respiration rate of hepatocytes from mammals of different body mass, Am. J. Physiol., 269, 1213

Porter, 1993, Body mass dependence of H+ leak in mitochondria and its relevance to metabolic rate, Nature, 362, 628, 10.1038/362628a0

Porter, 1996, Allometry of mitochondrial proton leak: influence of membrane surface area and fatty acid composition, Am. J. Physiol., 271, 1550

Powers, 2008, Cerebral mitochondrial metabolism in early Parkinson's disease, J. Cereb. Blood Flow Metab., 28, 1754, 10.1038/jcbfm.2008.63

Przedborski, 2005, Reactive oxygen and nitrogen species: weapons of neuronal destruction in models of Parkinson's disease, Antioxid. Redox Signal., 7, 685, 10.1089/ars.2005.7.685

Ramsey, 2004, Proton leak and hydrogen peroxide production in liver mitochondria from energy-restricted rats, Am. J. Physiol. Endocrinol. Metab., 286, E31, 10.1152/ajpendo.00283.2003

Rasbach, 2007, PGC-1alpha over-expression promotes recovery from mitochondrial dysfunction and cell injury, Biochem. Biophys. Res. Commun., 355, 734, 10.1016/j.bbrc.2007.02.023

Reznick, 2007, Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis, Cell Metab., 5, 151, 10.1016/j.cmet.2007.01.008

Richard, 2001, Uncoupling protein 2 in the brain: distribution and function, Biochem. Soc. Trans., 29, 812, 10.1042/bst0290812

Richter, 1988, Normal oxidative damage to mitochondrial and nuclear DNA is extensive, Proc. Natl. Acad. Sci. U.S.A., 85, 6465, 10.1073/pnas.85.17.6465

Ricquier, 2000, Mitochondrial uncoupling proteins: from mitochondria to the regulation of energy balance, J. Physiol., 529, 3, 10.1111/j.1469-7793.2000.00003.x

Rohas, 2007, A fundamental system of cellular energy homeostasis regulated by PGC-1alpha, Proc. Natl. Acad. Sci. U.S.A., 104, 7933, 10.1073/pnas.0702683104

Rolfe, 1996, Proton leak and control of oxidative phosphorylation in perfused, resting rat skeletal muscle, Biochim. Biophys. Acta, 1276, 45, 10.1016/0005-2728(96)00029-1

Rolfe, 1997, The physiological significance of mitochondrial proton leak in animal cells and tissues, Biosci. Rep., 17, 9, 10.1023/A:1027327015957

Rolfe, 1997, Cellular energy utilization and molecular origin of standard metabolic rate in mammals, Physiol. Rev., 77, 731, 10.1152/physrev.1997.77.3.731

Rosen, 1993, Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis, Nature, 362, 59, 10.1038/362059a0

Sanchis, 1998, BMCP1, a novel mitochondrial carrier with high expression in the central nervous system of humans and rodents, and respiration uncoupling activity in recombinant yeast, J. Biol. Chem., 273, 34611, 10.1074/jbc.273.51.34611

Sasaki, 1996, Ultrastructural study of synapses in the anterior horn neurons of patients with amyotrophic lateral sclerosis, Neurosci. Lett., 204, 53, 10.1016/0304-3940(96)12314-4

Scarpace, 1998, Leptin induction of UCP1 gene expression is dependent on sympathetic innervation, Am. J. Physiol., 275, E259

Schapira, 1992, Mitochondrial function in Parkinson's disease. The Royal Kings and Queens Parkinson's Disease Research Group, Ann. Neurol., 32, 116, 10.1002/ana.410320720

Schrauwen, 2001, Uncoupling protein 3 content is decreased in skeletal muscle of patients with type 2 diabetes, Diabetes, 50, 2870, 10.2337/diabetes.50.12.2870

Schrauwen, 2006, Putative function and physiological relevance of the mitochondrial uncoupling protein-3: involvement in fatty acid metabolism?, Prog. Lipid. Res., 45, 17, 10.1016/j.plipres.2005.11.001

Schriner, 2005, Extension of murine life span by overexpression of catalase targeted to mitochondria, Science, 308, 1909, 10.1126/science.1106653

Serviddio, 2007, Bioenergetics in aging: mitochondrial proton leak in aging rat liver, kidney and heart, Redox Rep., 12, 91, 10.1179/135100007X162112

Short, 2001, T(3) increases mitochondrial ATP production in oxidative muscle despite increased expression of UCP2 and -3, Am. J. Physiol. Endocrinol. Metab., 280, E761, 10.1152/ajpendo.2001.280.5.E761

Siklos, 1996, Ultrastructural evidence for altered calcium in motor nerve terminals in amyotropic lateral sclerosis, Ann. Neurol., 39, 203, 10.1002/ana.410390210

Skulachev, 1996, Role of uncoupled and non-coupled oxidations in maintenance of safely low levels of oxygen and its one-electron reductants, Q. Rev. Biophys., 29, 169, 10.1017/S0033583500005795

Skulachev, 1998, Uncoupling: new approaches to an old problem of bioenergetics, Biochim. Biophys. Acta, 1363, 100, 10.1016/S0005-2728(97)00091-1

Smith, 1991, Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease, Proc. Natl. Acad. Sci. U.S.A., 88, 10540, 10.1073/pnas.88.23.10540

Sohal, 1994, Effect of age and caloric restriction on DNA oxidative damage in different tissues of C57BL/6 mice, Mech. Ageing Dev., 76, 215, 10.1016/0047-6374(94)91595-4

Sohal, 1994, Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse, Mech. Ageing Dev., 74, 121, 10.1016/0047-6374(94)90104-X

Sohal, 1996, Oxidative stress, caloric restriction, and aging, Science, 273, 59, 10.1126/science.273.5271.59

Solans, 2006, Cytotoxicity of a mutant huntingtin fragment in yeast involves early alterations in mitochondrial OXPHOS complexes II and III, Hum. Mol. Genet., 15, 3063, 10.1093/hmg/ddl248

Souza, 2000, Dityrosine cross-linking promotes formation of stable alpha-synuclein polymers. Implication of nitrative and oxidative stress in the pathogenesis of neurodegenerative synucleinopathies, J. Biol. Chem., 275, 18344, 10.1074/jbc.M000206200

Speakman, 2004, Uncoupled and surviving: individual mice with high metabolism have greater mitochondrial uncoupling and live longer, Aging Cell, 3, 87, 10.1111/j.1474-9728.2004.00097.x

Stadtman, 1992, Protein oxidation and aging, Science, 257, 1220, 10.1126/science.1355616

Starkov, 2003, Regulation of brain mitochondrial H2O2 production by membrane potential and NAD(P)H redox state, J. Neurochem., 86, 1101, 10.1046/j.1471-4159.2003.01908.x

Stöckl, 2007, Partial uncoupling of oxidative phosphorylation induces premature senescence in human fibroblasts and yeast mother cells, Free Radic. Biol. Med., 43, 947, 10.1016/j.freeradbiomed.2007.06.005

Stout, 1998, Glutamate-induced neuron death requires mitochondrial calcium uptake, Nat. Neurosci., 1, 366, 10.1038/1577

Stuart, 2005, No evidence of mitochondrial respiratory dysfunction in OGG1-null mice deficient in removal of 8-oxodeoxyguanine from mitochondrial DNA, Free Radic. Biol. Med., 38, 737, 10.1016/j.freeradbiomed.2004.12.003

Stuart, 1999, Mitochondrial proton leak and the uncoupling proteins, J. Bioenerg. Biomembr., 31, 517, 10.1023/A:1005456725549

Stuart, 2001, Mitochondrial proton leak and the uncoupling protein 1 homologues, Biochim. Biophys. Acta, 1504, 144, 10.1016/S0005-2728(00)00243-7

Stuart, 1999, Uncoupling protein 2 from carp and zebrafish, ectothermic vertebrates, Biochim. Biophys. Acta, 1413, 50, 10.1016/S0005-2728(99)00081-X

Stuart, 2001, A mitochondrial uncoupling artifact can be caused by expression of uncoupling protein 1 in yeast, Biochem. J., 356, 779, 10.1042/0264-6021:3560779

Sugars, 2003, Transcriptional abnormalities in Huntington disease, Trends Genet., 19, 233, 10.1016/S0168-9525(03)00074-X

Sullivan, 2003, Mitochondrial uncoupling protein-2 protects the immature brain from excitotoxic neuronal death, Ann. Neurol., 53, 711, 10.1002/ana.10543

Tabrizi, 1999, Biochemical abnormalities and excitotoxicity in Huntington's disease brain, Ann. Neurol., 45, 25, 10.1002/1531-8249(199901)45:1<25::AID-ART6>3.0.CO;2-E

Talbot, 2004, Production of endogenous matrix superoxide from mitochondrial complex I leads to activation of uncoupling protein 3, FEBS Lett., 556, 111, 10.1016/S0014-5793(03)01386-3

Tissenbaum, 2001, Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans, Nature, 410, 227, 10.1038/35065638

Tretter, 2007, Uncoupling is without an effect on the production of reactive oxygen species by in situ synaptic mitochondria, J. Neurochem., 103, 1864, 10.1111/j.1471-4159.2007.04891.x

Turrens, 2003, Mitochondrial formation of reactive oxygen species, J. Physiol., 552, 335, 10.1113/jphysiol.2003.049478

Turrens, 1980, Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria, Biochem. J., 191, 421, 10.1042/bj1910421

Van Voorhies, 2003, Is life span extension in single gene long-lived Caenorhabditis elegans mutants due to hypometabolism?, Exp. Gerontol., 38, 615, 10.1016/S0531-5565(03)00070-6

Vidal-Puig, 2000, Energy metabolism in uncoupling protein 3 gene knockout mice, J. Biol. Chem., 275, 16258, 10.1074/jbc.M910179199

Vogler, 2006, Uncoupling protein 2 has protective function during experimental autoimmune encephalomyelitis, Am. J. Pathol., 168, 1570, 10.2353/ajpath.2006.051069

Wang, 2005, The orphan nuclear receptor SHP regulates PGC-1alpha expression and energy production in brown adipocytes, Cell Metab., 2, 227, 10.1016/j.cmet.2005.08.010

Warburg, 1956, On respiratory impairment in cancer cells, Science, 124, 269, 10.1126/science.124.3215.269

Wei, 2009, The brain uncoupling protein UCP4 attenuates mitochondrial toxin-induced cell death: role of extracellular signal-regulated kinases in bioenergetics adaptation and cell survival, Neurotox. Res., 16, 14, 10.1007/s12640-009-9039-8

Weindruch, 1986, The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake, J. Nutr., 116, 641, 10.1093/jn/116.4.641

Weydt, 2006, Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration, Cell Metab., 4, 349, 10.1016/j.cmet.2006.10.004

Wiedemann, 2002, Mitochondrial DNA and respiratory chain function in spinal cords of ALS patients, J. Neurochem., 80, 616, 10.1046/j.0022-3042.2001.00731.x

Wisniewski, 2008, Preventing beta-amyloid fibrillization and deposition: beta-sheet breakers and pathological chaperone inhibitors, BMC Neurosci., 9, S5, 10.1186/1471-2202-9-S2-S5

Wolkow, 2000, Regulation of C. elegans life-span by insulinlike signaling in the nervous system, Science, 290, 147, 10.1126/science.290.5489.147

Wu, 1999, Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1, Cell, 98, 115, 10.1016/S0092-8674(00)80611-X

Xiao, 2004, Expression of lung uncoupling protein-2 mRNA is modulated developmentally and by caloric intake, Exp. Biol. Med. (Maywood), 229, 479, 10.1177/153537020422900605

Yu, 1992, Effect of age-related lipid peroxidation on membrane fluidity and phospholipase A2: modulation by dietary restriction, Mech. Ageing Dev., 65, 17, 10.1016/0047-6374(92)90123-U

Yu, 2000, Characterization of novel UCP5/BMCP1 isoforms and differential regulation of UCP4 and UCP5 expression through dietary or temperature manipulation, FASEB J., 14, 1611, 10.1096/fj.14.11.1611

Zhang, 2001, Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, β cell dysfunction, and Type 2 diabetes, Cell, 105, 745, 10.1016/S0092-8674(01)00378-6

Zhang, 2006, Genipin inhibits UCP2-mediated proton leak and acutely reverses obesity- and high glucose-induced beta cell dysfunction in isolated pancreatic islets, Cell Metab., 3, 417, 10.1016/j.cmet.2006.04.010