Page 1, 2, 3
1. Chen Q et al. Production of reactive oxygen species by mitochondria. Central role of Complex III. J Biol Chem. September 19, 2003;278:36027–36031.
2. Americans eat their weight in genetically engineered food [online press release]. Environmental Working Group. http://www.ewg.org/release/americans-eat-their-weight-genetically-engineered-food. Accessed October 30, 2014.
3. Majewski MS et al. Pesticides in Mississippi air and rain: a comparison between 1995 and 2007. Environ Toxicol Chem. 2014 Jun;33(6):1283–1293.
4. Mesnage R et al. Ethoxylated adjuvants of glyphosate-based herbicides are active principles of human cell toxicity. Toxicology. 2013;313(2–3):122–128.
5. Mesnage R et al. Major pesticides are more toxic to human cells than their declared active principles. Biomed Res Int. 2014. Article ID 179691. Available at http://dx.doi.org/10.1155/2014/179691.
6. Peixoto F. Comparative effects of the Roundup and glyphosate on mitochondrial oxidative phosphorylation. Chemosphere. 2005 Dec;61(8):1115–1122.
7. Koller VJ et al. Cytotoxic and DNA-damaging properties of glyphosate and Roundup in human-derived buccal epithelial cells. Arch Toxicol. 2012 May;86(5):805–813.
8. Madrigal JL et al. Glutathione depletion, lipid peroxidation and mitochondrial dysfunction are induced by chronic stress in rat brain. Neuropsychopharmacology. 2001 Apr;24(4):420–429.
9. Beal MF. Mitochondria, free radicals, and neurodegeneration. Curr Opin Neurobiol. 1996 Oct;6(5):661–666.
10. Morava E, Kozicz T. Mitochondria and the economy of stress (mal)adaptation. Neurosci Biobehav Rev. 2013 May;37(4):668–680.
11. Mortensen OH et al. Developmental programming by high fructose decreases phosphorylation efficiency in aging offspring brain mitochondria, correlating with enhanced UCP5 expression. J Cereb Blood Flow Metab. 2014 Jul;34(7):1205–1211.
12. Lustig RH. Fructose: it's "alcohol without the buzz." Adv Nutr. 2013 Mar 1;4(2):226–235.
13. Neustadt J, Pieczenik SR. Medication-induced mitochondrial damage and disease. Mol Nutr Food Res. 2008;52:780–788.
14. Grossniklaus U et al. Transgenerational epigenetic inheritance: how important is it? Nat Rev Genet. 2013;14:228–235.
15. Adam M et al. Epigenetic inheritance based evolution of antibiotic resistance in bacteria. BMC Evol Biol. 2008;8:52
16. Feinberg AP. Phenotypic plasticity and the epigenetics of human disease. Nature. 2007;447:433–440.
17. Rogina B, Helfand SL. Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci U S A. 2004;101(45):15998–16003.
18. Wood JG et al. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature. 2004;430(7000):686–689.
19. Guarente L, Kenyon C. Genetic pathways that regulate ageing in model organisms. Nature. 2000;408(6809):255–262.
20. Guarente L. Mitochondria – a nexus for aging, calorie restriction, and sirtuins? Cell. 2008;132(2):171–176.
21. Lombard DB et al. SIRT6 in DNA repair, metabolism and ageing. J Intern Med. 2008;263(2):128–141.
22. Kim HS et al. SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress. Cancer Cell. 2010;17(1):41–52.
23. Qiu X et al. Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. Cell Metab. 2010;12(6):662–667.
24. Tao R et al. Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stress. Mol Cell. 2010;40(6):893–904.
25. Someya S et al. Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell. 2010;143(5):802–812.
26. Zhu Y et al. SIRT3 and SIRT4 are mitochondrial tumor suppressor proteins that connect mitochondrial metabolism and carcinogenesis. Cancer Metab. 2014 Oct 20;2:15. doi:10.1186/2049-3002-2-15. eCollection 2014.
27. Singh KK. Mitochondrial dysfunction is a common phenotype in aging and cancer. Ann N Y Acad Sci. 2004;1019:260–264.
28. Afanas'Ev IB. Mechanism of superoxide-mediated damage relevance to mitochondrial aging. Ann N Y Acad Sci. 2004;1019:343–345.
29. Berneburg M et al. Repair of mitochondrial DNA in aging and carcinogenesis. Photochem Photobiol Sci. 2006;5(2):190–198.
30. Singh KK. Mitochondria damage checkpoint, aging, and cancer. Ann N Y Acad Sci. 2006;1067:182–190.
31. Dai D-F et al. Mitochondria and cardiovascular aging. Circ Res.2012;110:1109–1124.
32. Ershler WB, Longo DL. Aging and cancer: issues of basic and clinical science. J Natl Cancer Inst. 1997;89(20):1489–1497.
33. Ershler WB, Longo DL. The biology of aging: the current research agenda. Cancer. 1997;80(7):1284–1293.
34. Ahn BH et al. A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc Natl Acad Sci U S A. 2008;105(38):14447–14452.
35. Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956;11(3):298–300.
36. Rossignol DA, Frye RE. Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry. 2012;17:290–314.
37. Rose S et al. Oxidative stress induces mitochondrial dysfunction in a subset of autistic lymphoblastoid cell lines. Transl Psychiatry. April 1, 2014;4(4):e377.
38. Samavati L et al. Tumor necrosis factor alpha inhibits oxidative phosphorylation through tyrosine phosphorylation at subunit I of cytochrome c oxidase. J Biol Chem. 2008;283:21134–21344.
39. Vempati UD et al. Role of cytochrome C in apoptosis: increased sensitivity to tumor necrosis factor alpha is associated with respiratory defects but not with lack of cytochrome C release. Mol Cell Biol. 2007;27:1771–1783.
40. Suematsu N et al. Oxidative stress mediates tumor necrosis factor-alpha-induced mitochondrial DNA damage and dysfunction in cardiac myocytes. Circulation. 2003;107:1418–1423.
41. Anitha A et al. Downregulation of the expression of mitochondrial electron transport complex genes in autism brains. Brain Pathol. 2013;23(3):294–302.
42. Napoli E et al. Evidence of reactive oxygen species-mediated damage to mitochondrial DNA in children with typical autism. Mol Autism. 2013;4(1):2.
43. Ross-Inta C et al. Evidence of mitochondrial dysfunction in fragile X-associated tremor/ataxia syndrome. Biochem J. 2010;429(3):545–552.
44. Andreazza AC et al. Specific subcellular changes in oxidative stress in prefrontal cortex from patients with bipolar disorder. J Neurochem. 2013;127(4):552–561.
45. Ben-Shachar D, Karry R. Neuroanatomical pattern of mitochondrial complex I pathology varies between schizophrenia, bipolar disorder and major depression. PLoS ONE. 2008;3(11)e3676.
46. Gubert C et al. Mitochondrial activity and oxidative stress markers in peripheral blood mononuclear cells of patients with bipolar disorder, schizophrenia, and healthy subjects. J Psychiatric Res. 2013;47(10):1396–1402.
47. Orhan N et al. Genetic variants in nuclear-encoded mitochondrial proteins are associated with oxidative stress in obsessive compulsive disorders. J Psychiatric Res. 2012;46(2):212–218.
48. Di Lisa F et al. Mitochondria and vascular pathology. Pharmacol Rep. 2009;61(1):123–130.
49. Perrotta I et al. MnSOD expression in human atherosclerotic plaques: an immunohistochemical and ultrastructural study. Cardiovasc Pathol. 2013;22(6):428–437.
50. Sobenin IA et al. Changes of mitochondria in atherosclerosis: possible determinant in the pathogenesis of the disease. Atherosclerosis. 2013;227(2):283–238.
51. Guzik B et al. Mechanisms of oxidative stress in human aortic aneurysms – association with clinical risk factors for atherosclerosis and disease severity. Int J Cardiol. 2013;168(3):2389–2396.
52. Hansel B et al. Metabolic syndrome is associated with elevated oxidative stress and dysfunctional dense high-density lipoprotein particles displaying impaired antioxidative activity. J Clin Endocrinol Metab. 2004;89(10):4963–4971.
53. Palmieri VO et al. Systemic oxidative alterations are associated with visceral adiposity and liver steatosis in patients with metabolic syndrome. J Nutr. 2006;136(12):3022–3026.
54. Koene S et al. Natural disease course and genotype-phenotype correlations in Complex I deficiency caused by nuclear gene defects: what we learned from 130 cases. J Inherit Metab Dis. 2012;35(5):737–747.
55. Huang C et al. Depleted leukocyte mitochondrial DNA copy number in metabolic syndrome. J Atheroscler Thromb. 2011;18(10):867–873.
56. Mitchell T, Darley-Usmar V. Metabolic syndrome and mitochondrial dysfunction: insights from preclinical studies with a mitochondrially targeted antioxidant. Free Radic Biol Med. 2012;52(5):838–840.
57. Picard M et al. Mitochondrial allostatic load puts the 'gluc' back in glucocorticoids. Nat Rev Endocrinol. 2014 May;10(5):303–310.
58. Amer MA et al. Influence of glutathione S-transferase polymorphisms on type-2 diabetes mellitus risk. Genet Mol Res. 2011;10(4):3722–3730.
59. Khan S et al. Role and clinical significance of lymphocyte mitochondrial dysfunction in type 2 diabetes mellitus. Transl Res. 2011;158(6):344–359.
60. Avila C et al. Platelet mitochondrial dysfunction is evident in type 2 diabetes in association with modifications of mitochondrial anti-oxidant stress proteins. Exp Clin Endocrinol Diabetes. 2012;120(4):248–251.
61. Calabrese V et al. Oxidative stress, glutathione status, sirtuin and cellular stress response in type 2 diabetes. Biochim Biophys Acta BBA. 2012;1822(5):729–736.
62. Gray SP et al. NADPH oxidase 1 plays a key role in diabetes mellitus-accelerated atherosclerosis. Circulation. 2013;127(18):1888–1902.
63. Pagano G et al. From clinical description to in vitro and animal studies, and backwards to patients: oxidative stress and mitochondrial dysfunction in Fanconi anemia. Free Radic Biol Med. 2013;58:118–125.
64. Pagano G et al. Multiple involvement of oxidative stress in Werner syndrome phenotype. Biogerontology. 2005;6(4):233–243.
65. Kulich SM et al. 6-Hydroxydopamine induces mitochondrial ERK activation. Free Radic Biol Med. 2007;43:372–383.
66. Wang DM et al. Effects of long-term treatment with quercetin on cognition and mitochondrial function in a mouse model of Alzheimer's disease. Neurochem Res. Epub 2014 Jun 4.
67. Area-Gomez E et al. Upregulated function of mitochondria-associated ER membranes in Alzheimer disease. EMBO J. 2012;31(21):4106–4123.
68. Atamna H et al. Mechanisms of mitochondrial dysfunction and energy deficiency in Alzheimer's disease. Mitochondrion. 2007;7(5):297–310.
69. Dumont M et al. Coenzyme Q(10) decreases amyloid pathology and improves behavior in a transgenic mouse model of Alzheimer's disease. J Alzheimers Dis. 2011;27(1):211–223.
70. Murakami K et al. Stimulation of the amyloidogenic pathway by cytoplasmic superoxide radicals in an Alzheimer's disease mouse model. Biosci Biotechnol Biochem. 2012;76(6):1098–1103.
71. Hardas SS et al. Oxidative modification of lipoic acid by HNE in Alzheimer disease brain. Redox Biol. 2013;1(1):80–85.
72. Aliev G et al. Oxidative stress induced mitochondrial failure and vascular hypoperfusion as a key initiator for the development of Alzheimer disease. Pharmaceuticals. 2010;3(1):158–187.
73. Li Z et al. Mitochondrial genome sequencing of chondrocytes in osteoarthritis by human mitochondria RT2 Profiler PCR array. Mol Med Rep. 2012;6(1):39–44.
74. Fernández-Moreno M et al. Mitochondrial haplogroups define two phenotypes of osteoarthritis. Front Physiol. 2012;3(article 129).
75. Gavrilidis C et al. Mitochondrial dysfunction in osteoarthritis is associated with down-regulation of superoxide dismutase 2. Arthritis Rheum. 2013;65(5):378–387.
76. Pagano G et al. Oxidative stress and mitochondrial dysfunction across broad-ranging pathologies: toward mitochondria-targeted clinical strategies. Oxid Med Cell Longev. May 4, 2014;2014:541230. doi:10.1155/2014/541230.
77. Kim YS et al. Can mitochondrial dysfunction be a predictive factor for oxidative stress in patients with obstructive sleep apnea? Antioxid Redox Signal. 2014 Sep 20;21(9):1285–1288.
78. Ramalho-Santos J, Amaral S. Mitochondria and mammalian reproduction. Mol Cell Endocrinol. 2013 Oct 15;379(1–2):74–84.
79. Strushkevich N et al. Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system. Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10139–10143.
80. Le B et al. New targets for increasing endogenous testosterone production: clinical implications and review of the literature. Andrology. Epub 2014 May 12.
81. Psarra AG et al. Steroid and thyroid hormone receptors in mitochondria. IUBMB Life. April 2008. 60(4):210–223.
82. Wickramasekera NT, Das GM. Tumor suppressor p53 and estrogen receptors in nuclear-mitochondrial communication. Mitochondrion. 2014 May;16C:26–37.
83. Vasconsuelo A et al. Role of 17b-estradiol and testosterone in apoptosis. Steroids. 2011 Nov;76(12):1223–1231.
84. Gigli I, Bussmann LE. Exercise and ovarian steroid hormones: their effects on mitochondrial respiration. Life Sci. 2001;68(13):1505–1514.
85. Klinge CM. Estrogenic control of mitochondrial function and biogenesis. J Cell Biochem. 2008;105(6):1342–1351.
86. Kulinsky VI, Kolesnichenko LS. Biochemistry (Moscow) Supplement Series B: Biomed Chem. June 2007;1(2):95–113.
87. Lange C et al. Estrogenic activity of constituents of underarm deodorants determined by E-Screen assay. Chemosphere. 2014 Aug;108:101–106.
88. Fujino C et al. Transesterification of a series of 12 parabens by liver and small-intestinal microsomes of rats and humans. Food Chem Toxicol. 2014 Feb;64:361–368.
89. Nakagawa Y and Moore G. Role of mitochondrial membrane permeability transition in p-hydroxybenzoate ester-induced cytotoxicity in rat hepatocytes. Biochem Pharmacol. 1999 Sep 1;58(5):811–816.
90. Haas RH et al. The in-depth evaluation of suspected mitochondrial disease. Mol Genet Metab. May 2008;94(1):16–37.
91. Bough KJ et al. Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet. Ann Neurol. 2006;60(2):223–235.
92. Hughes SD et al. The ketogenic diet component decanoic acid increases mitochondrial citrate synthase and complex I activity in neuronal cells. J Neurochem. 2014;129:426–433.
93. Nylen K et al. A ketogenic diet rescues the murine succinic semialdehyde dehydrogenase deficient phenotype. Exp Neurol. 2008 Apr;210(2):449–457.
94. Barnerias C et al. Pyruvate dehydrogenase complex deficiency: four neurological phenotypes with differing pathogenesis. Dev Med Child Neurol. 2010 Feb;52(2):e1–9.
95. Wexler ID et al. Outcome of pyruvate dehydrogenase deficiency treated with ketogenic diets. Studies in patients with identical mutations. Neurology. 1997 Dec;49(6):1655–1661.
96. Gonçalves IO et al. Physical exercise prevents and mitigates non-alcoholic steatohepatitis-induced liver mitochondrial structural and bioenergetics impairments. Mitochondrion. 2014 Mar;15:40–51.
97. Nicolson GL. Mitochondrial dysfunction and chronic disease: treatment with natural supplements. Altern Ther Health Med. 2014 Winter;20 Suppl 1:18–25.
98. Jiang T et al. Lipoic acid restores age-associated impairment of brain energy metabolism through the modulation of Akt/JNK signaling and PGC1a transcriptional pathway. Aging Cell. 2013 Dec;12(6):1021–1031.
99. Zhou L et al. a-Lipoic acid ameliorates mitochondrial impairment and reverses apoptosis in FABP3-overexpressing embryonic cancer cells. J Bioenerg Biomembr. 2013 Oct;45(5):459–466.
100 Tarnopolsky MA. The mitochondrial cocktail: rationale for combined nutraceutical therapy in mitochondrial cytopathies. Adv Drug Deliv Rev. 2008 Oct–Nov;60(13–14):1561–1567.
101. Komura K et al. Effectiveness of creatine monohydrate in mitochondrial encephalomyopathies. Pediatr Neurol. 2003 Jan;28(1):53–58.
102. Tsagris V, Liapi-Adamidou G. Serum carnitine levels in patients with homozygous beta thalassemia: a possible new role for carnitine? Eur J Pediatr. 2005 Mar;164(3):131–134.
103. Kathirvel E et al. Acetyl-L-carnitine and lipoic acid improve mitochondrial abnormalities and serum levels of liver enzymes in a mouse model of nonalcoholic fatty liver disease. Nutr Res. 2013 Nov;33(11):932–941.
104. Pesce V et al. Acetyl-L-carnitine activates the peroxisome proliferator-activated receptor-g coactivators PGC-1a/PGC-1b-dependent signaling cascade of mitochondrial biogenesis and decreases the oxidized peroxiredoxins content in old rat liver. Rejuvenation Res. 2012 Apr;15(2):136–139.
105. Patel SP et al. N-acetylcysteine amide preserves mitochondrial bioenergetics and improves functional recovery following spinal trauma. Exp Neurol. 2014 Jul;257:95–105.
106. Feldkamp T et al. Preservation of complex I function during hypoxia-reoxygenation-induced mitochondrial injury in proximal tubules. Am J Physiol Renal Physiol. 2004 Apr;286(4):F749–59.
107. Ferretta A et al. Effect of resveratrol on mitochondrial function: implications in parkin-associated familiar Parkinson's disease. Biochim Biophys Acta. 2014 Jul;1842(7):902–915.
108. Lin CJ et al. Resveratrol protects astrocytes against traumatic brain injury through inhibiting apoptotic and autophagic cell death. Cell Death Dis. 2014 Mar 27;5:e1147.
109. Beaudoin MS et al. Impairments in mitochondrial palmitoyl-CoA respiratory kinetics that precede development of diabetic cardiomyopathy are prevented by resveratrol in ZDF rats. J Physiol. 2014 Jun 15;592(Pt 12):2519–2533.
110. Weimer S et al. D-Glucosamine supplementation extends life span of nematodes and of ageing mice. Nat Commun.2014 Apr 8;5:3563.
111. Wang et al. Op cit.
112. Weber H et al. Beneficial effect of the bioflavonoid quercetin on cholecystokinin-induced mitochondrial dysfunction in isolated rat pancreatic acinar cells. Can J Physiol Pharmacol. 2014 Mar;92(3):215–225.
113. Stanely MPP. (-) Epicatechin attenuates mitochondrial damage by enhancing mitochondrial multi-marker enzymes, adenosine triphosphate and lowering calcium in isoproterenol induced myocardial infarcted rats. Food Chem Toxicol. 2013 Mar;53:409–416.
114. Panasiuk OS et al. The influence of dietary omega-3 polyunsaturated fatty acids on functional parameters of myocardial mitochondria during isoproterenol-induced heart injury. [Article in Ukrainian.] Fiziol Zh. 2014;60(1):18–24.
Dr. Chris D. Meletis is an educator, international author, and lecturer. His personal mission is "Changing America's Health One Person at a Time." He believes that when people become educated about their bodies, that is the moment when true change and wellness begins. Dr. Meletis served as dean of naturopathic medicine and chief medical officer for 7 years at National College of Natural Medicine (NCNM) and was awarded the 2003 Physician of the Year award by the American Association of Naturopathic Physicians. www.DrMeletis.com.
Kimberly Wilkes is a freelance writer specializing in health, science, nutrition, and complementary medicine. She has written more than 300 articles covering a variety of topics from the dangers of homocysteine to sugar's damaging effects on the heart. She is the editor of Complementary Prescriptions Journal and enjoys scouring the medical literature to find the latest health-related science.
Page 1, 2, 3