Mitochondrial dysfunction in cancer and neurodegenerative diseases: Spotlight on fatty acid oxidation and lipoperoxidation products

Antioxidants

Volumn 5, Issue 1, 2016, Pages

  Barrera, Giuseppina ^a   Gentile, Fabrizio ^b   Pizzimenti, Stefania ^a   Canuto, Rosa Angela ^a   Daga, Martina ^a   Arcaro, Alessia ^b   Cetrangolo, Giovanni Paolo ^b   Lepore, Alessio ^c   Ferretti, Carlo ^a   Dianzani, Chiara ^a   Muzio, Giuliana ^a  

^a UNIVERSITY OF TURIN   (Italy)

^b UNIVERSITY OF MOLISE   (Italy)

^c UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

Cancer; Fatty acid oxidation; Lipoperoxidation products; Mitochondria; Neurodegenerative diseases

Indexed keywords

EID: 85010366340     PISSN: None     EISSN: 20763921     Source Type: Journal    
DOI: 10.3390/antiox5010007     Document Type: Review

References (157)

1. Pandey, P.R.; Liu, W.; Xing, F.; Fukuda, K.; Watabe, K. Anti-cancer drugs targeting fatty acid synthase (FAS). Recent Pat. Anticancer Drug Discov. 2012, 7, 185–197.
2. Wise, D.R.; Thompson, C.B. Glutamine addiction: A new therapeutic target in cancer. Trends Biochem. Sci. 2010, 35, 427–433.
3. Warburg, O. On the origin of cancer cells. Science 1956, 123, 309–314.
4. Zhang, S.; Yang, C.; Yang, Z.; Zhang, D.; Ma, X.; Mills, G.; Liu, Z. Homeostasis of redox status derived from glucose metabolic pathway could be the key to understanding the Warburg effect. Am. J. Cancer Res. 2015, 5, 1265–1280.
5. Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell 2011, 144, 646–674.
6. Samudio, I.; Harmancey, R.; Fiegl, M.; Kantarjian, H.; Konopleva, M.; Korchin, B.; Kaluarachchi, K.; Bornmann, W.; Duvvuri, S.; Taegtmeyer, H.; et al. Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction. J. Clin. Investig. 2010, 120, 142–156.
7. Tirado-Vélez, J.M.; Joumady, I.; Sáez-Benito, A.; Cózar-Castellano, I.; Perdomo, G. Inhibition of fatty acid metabolism reduces human myeloma cells proliferation. PLoS ONE 2012, 7.
8. West, D.; Marnett, L.J. Endogenous reactive intermediates as modulators of cell signaling and cell death. Chem. Res. Toxicol. 2006, 19, 173–194.
9. Barrera, G.; Pizzimenti, S.; Ciamporcero, E.S.; Daga, M.; Ullio, C.; Arcaro, A.; Cetrangolo, G.P.; Ferretti, C.; Dianzani, C.; Lepore, A.; Gentile, F. Role of 4-hydroxynonenal-protein adducts in human diseases. Antioxid. Redox Signal. 2015, 22, 1681–1702.
10. Chandra, D.; Singh, K.K. Genetic insights into OXPHOS defect and its role in cancer. Biochim. Biophys. Acta 2011, 1807, 620–625.
11. Yadav, N.; Chandra, D. Mitochondrial DNA mutations and breast tumorigenesis. Biochim. Biophys. Acta 2013, 1836, 336–344.
12. Wallace, D.C. Mitochondria and cancer. Nat. Rev. Cancer 2012, 12, 685–698.
13. Jang, M.; Kim, S.S.; Lee, J. Cancer cell metabolism: Implications for therapeutic targets. Exp. Mol. Med. 2013, 45.
14. Yadava, N.; Schneider, S.S.; Jerry, D.J.; Kim, C. Impaired mitochondrial metabolism and mammary carcinogenesis. J. Mammary Gland Biol. Neoplasia 2013, 18, 75–87.
15. Brand, K.A.; Hermfisse, U. Aerobic glycolysis by proliferating cells: A protective strategy against reactive oxygen species. FASEB J. 1997, 11, 388–395.
16. Sabharwal, S.S.; Schumacker, P.T. Mitochondrial ROS in cancer: Initiators, amplifiers or an Achilles’ heel? Nat. Rev. Cancer. 2014, 14, 709–721.
17. Viale, A.; Corti, D.; Draetta, G.F. Tumors and Mitochondrial Respiration: A Neglected Connection. Cancer Res. 2015, 75, 3685–3686.
18. Xekouki, P.; Stratakis, C.A. Succinate dehydrogenase (SDHx) mutations in pituitary tumors: Could this be a new role for mitochondrial complex II and/or Krebs cycle defects? Endocrinol. Relat. Cancer 2012, 19.
19. Yang, M.; Soga, T.; Pollard, P.J.; Adam, J. The emerging role of fumarate as an oncometabolite. Front. Oncol. 2012, 2.
20. Mayr, J.A.; Meierhofer, D.; Zimmerman, F.; Feichtinger, R.; Kögler, C.; Ratschek, M.; Schmeller, N.; Sperl, W.; Kofler, B. Loss of complex I due to mitochondrial DNA mutations in renal oncocytoma. Clin. Cancer Res. 2008, 14, 2270–2275.
21. Chiaradonna, F.; Gaglio, D.; Vanoni, M.; Alberghina, L. Expression oftransforming K-Ras oncogene affects mitochondrial function and morphologyin mouse fibroblasts. Biochim. Biophys. Acta 2006, 1757, 1338–1356.
22. Fridovich, I. Superoxide radical and superoxide dismutases. Annu. Rev. Biochem. 1995, 64, 97–112.
23. Okado-Matsumoto, A.; Fridovich, I. Subcellular distribution of superoxide dismutase (SOD) in rat liver: Cu, Zn-SOD in mitochondria. J. Biol. Chem. 2001, 276, 38388–38393.
24. Weinberg, F.; Hamanaka, R.; Wheaton, W.W.; Weinberg, S.; Joseph, J.; Lopez, M.; Kalyanaraman, B.; Mutlu, G.M.; Budinger, G.R.; Chandel, N.S. Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc. Natl Acad. Sci. USA 2010, 107, 8788–8793.
25. +-dependent methylenetetrahydrofolate dehydrogenase cyclohydrolase are glycine auxotrophs. J. Biol. Chem. 2003, 278, 19436–19441.
26. Christensen, K.E.; Mackenzie, R.E. Mitochondrial methylenetetrahydrofolate dehydrogenase, methenyltetrahydrofolate cyclohydrolase, and formyltetrahydrofolate synthetases. Vitam. Horm. 2008, 79, 393–410.
27. Fan, J.; Ye, J.; Kamphorst, J.J.; Shlomi, T.; Thompson, C.B.; Rabinowitz, J.D. Quantitative flux analysis reveals folate-dependent NADPH production. Nature 2014, 510, 298–302.
28. Nilsson, R.; Jain, M.; Madhusudhan, N.; Sheppard, N.G.; Strittmatter, L.; Kampf, C.; Huang, J.; Asplund, A.; Mootha, V.K. Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer. Nat. Commun. 2014, 5.
29. Craigen, W.J. Mitochondrial DNA mutations: An overview of clinical and molecular aspects. Methods Mol. Biol. 2012, 837, 3–15.
30. He, Y.; Wu, J.; Dressman, D.C.; Iacobuzio-Donahue, C.; Markowitz, S.D.; Velculescu, V.E.; Diaz, L.A., Jr.; Kinzler, K.W.; Vogelstein, B.; Papadopoulos, N. Heteroplasmic mitochondrial DNA mutations in normal and tumour cells. Nature 2010, 464, 610–614.
31. Lynch, M.; Koskella, B.; Schaack, S. Mutation pressure and the evolution of organelle genomic architecture. Science 2006, 311, 1727–1730.
32. Johnson, A.A.; Johnson, K.A. Exonuclease proofreading by human mitochondrial DNA polymerase. J. Biol. Chem. 2001, 276, 38097–38107.
33. Kornberg, R.D. Chromatin structure: A repeating unit of histones and DNA. Science 1974, 184, 868–871.
34. Yakes, F.M.; van Houten, B. Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc. Natl. Acad. Sci. USA 1997, 94, 514–519.
35. Polyak, K.; Li, Y.; Zhu, H.; Lengauer, C.; Willson, J.K.; Markowitz, S.D.; Trush, M.A.; Kinzler, K.W.; Vogelstein, B. Somatic mutations of the mitochondrial genome in human colorectal tumours. Nat. Genet. 1998, 20, 291–293.
36. Kulawiec, M.; Salk, J.J.; Ericson, N.G.; Wanagat, J.; Bielas, J.H. Generation, function, and prognostic utility of somatic mitochondrial DNA mutations in cancer. Environ. Mol. Mutagen. 2010, 51, 427–439.
37. Liu, V.W.; Shi, H.H.; Cheung, A.N.; Chiu, P.M.; Leung, T.W.; Nagley, P.; Wong, L.C.; Ngan, H.Y. High incidence of somatic mitochondrial DNA mutations in human ovarian carcinomas. Cancer Res. 2001, 61, 5998–6001.
38. Van Gisbergen, M.W.; Voets, A.M.; Starmans, M.H.; de Coo, I.F.; Yadak, R.; Hoffmann, R.F.; Boutros, P.C.; Smeets, H.J.; Dubois, L.; Lambin, P. How do changes in the mtDNA and mitochondrial dysfunction influence cancer and cancer therapy? Challenges, opportunities and models. Mutat. Res. Rev. Mutat. Res. 2015, 764, 16–30.
39. Schon, E.A.; DiMauro, S.; Hirano, M. Human mitochondrial DNA: Roles of inherited and somatic mutations. Nat. Rev. Genet. 2012, 13, 878–890.
40. Petros, J.A.; Baumann, A.K.; Ruiz-Pesini, E.; Amin, M.B.; Sun, C.Q.; Hall, J.; Lim, S.; Issa, M.M.; Flanders, W.D.; Hosseini, S.H.; et al. mtDNA mutations increase tumorigenicity in prostate cancer. Proc. Natl. Acad. Sci. USA 2005, 102, 719–724.
41. Ishikawa, K.; Takenaga, K.; Akimoto, M.; Koshikawa, N.; Yamaguchi, A.; Imanishi, H.; Nakada, K.; Honma, Y.; Hayashi, J. ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis. Science 2008, 320, 661–664.
42. Sullivan, L.B.; Chandel, N.S. Mitochondrial reactive oxygen species and cancer. Cancer Metab. 2014, 2.
43. Schug, Z.T.; Frezza, C.; Galbraith, L.C.; Gottlieb, E. The music of lipids: How lipid composition orchestrates cellular behaviour. Acta Oncol. 2012, 51, 301–310.
44. Schenkel, L.C.; Bakovic, M. Formation and regulation of mitochondrial membranes. Int. J. Cell Biol. 2014, 2014.
45. Horvath, S.E.; Daum, G. Lipids of mitochondria. Prog. Lipid Res. 2013, 52, 590–614.
46. Daum, G.; Vance, J.E. Import of lipids into mitochondria. Prog. Lipid Res. 1997, 36, 103–130.
47. Ren, M.; Phoon, C.K.; Schlame, M. Metabolism and function of mitochondrial cardiolipin. Prog. Lipid Res. 2014, 55, 1–16.
48. Chu, C.T.; Ji, J.; Dagda, R.K.; Jiang, J.F.; Tyurina, Y.Y.; Kapralov, A.A.; Tyurin, V.A.; Yanamala, N.; Shrivastava, I.H.; Mohammadyani, D.; et al. Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells. Nat. Cell Biol. 2013, 15, 1197–1205.
49. Osman, C.; Voelker, D.R.; Langer, T. Making heads or tails of phospholipids in mitochondria. J. Cell Biol. 2011, 192, 7–16.
50. Shiao, Y.-J.; Vance, J.E. Evidence for an ethanolamine cycle: Differential recycling of the ethanolamine moiety of phosphatidylethanolamine derived from phosphatidylserine and ethanolamine. Biochem. J. 1995, 310, 673–679.
51. Liu, J.; Dai, Q.; Chen, J.; Durrant, D.; Freeman, A.; Liu, T.; Grossman, D.; Lee, R.M. Phospholipid scramblase 3 controls mitochondrial structure, function, and apoptotic response. Mol. Cancer Res. 2003, 1, 892–902.
52. Mayr, J.A. Lipid metabolism in mitochondrial membranes. J. Inherit. Metab. Dis. 2015, 38, 137–144.
53. Hovius, R.; Thijssen, J.; van der Linden, P.; Nicolay, K.; de Kruijff, B. Phospholipid asymmetry of the outer membrane of rat liver mitochondria. Evidence for the presence of cardiolipin on the outside of the outer membrane. FEBS Lett. 1993, 330, 71–76.
54. Holloway, G.P.; Fajardo, V.A.; McMeekin, L.; LeBlanc, P.J. Unsaturation of mitochondrial membrane lipids is related to palmitate oxidation in subsarcolemmal and intermyofibrillar mitochondria. J. Membr. Biol. 2012, 245, 165–176.
55. Yamaoka, S.; Urade, R.; Kito, M. Cardiolipin molecular species in rat heart mitochondria are sensitive to essential fatty acid-deficient dietary lipids. J. Nutr. 1990, 120, 415–421.
56. Fajardo, V.A.; McMeekin, L.; Saint, C.; LeBlanc, P.J. Cardiolipin linoleic acid content and mitochondrial cytochrome c oxidase activity are associated in rat skeletal muscle. Chem. Phys. Lipids 2015, 187, 50–55.
57. Soni, S.P.; LoCascio, D.S.; Liu, Y.; Williams, J.A.; Bittman, R.; Stillwell, W.; Wassall, S.R. Docosahexaenoic acid enhances segregation of lipids between: 2H-NMR study. Biophys. J. 2008, 95, 203–214.
58. Wang, H.Y.; Jackson, S.N.; Woods, A.S. Direct MALDI-MS analysis of cardiolipin from rat organs sections. J. Am. Soc. Mass. Spectrom. 2007, 18, 567–577.
59. Feillet-Coudray, C.; Fouret, G.; Casas, F.; Coudray, C. Impact of high dietary lipid intake and related metabolic disorders on the abundance and acyl composition of the unique mitochondrial phospholipid, cardiolipin. J. Bioenerg. Biomembr. 2014, 46, 447–457.
60. Guderley, H.; Kraffe, E.; Bureau, W.; Bureau, D.P. Dietary fatty acid composition changes mitochondrial phospholipids and oxidative capacities in rainbow trout red muscle. J. Comp. Physiol. 2008, 178, 385–399.
61. Hiltunen, J.K.; Chen, Z.; Haapalainen, A.M.; Wierenga, R.K.; Kastaniotis, A.J. Mitochondrial fatty acid synthesis—An adopted set of enzymes making a pathway of major importance for the cellular metabolism. Prog. Lipid Res. 2010, 49, 27–45.
62. Hiltunen, J.K.; Schonauer, M.S.; Autio, K.J.; Mittelmeier, T.M.; Kastaniotis, A.J.; Dieckmann, C.L. Mitochondrial fatty acid synthesis type II: More than just fatty acids. J. Biol. Chem. 2009, 284, 9011–9015.
63. Stavrovskaya, I.G.; Bird, S.S.; Marur, V.R.; Sniatynski, M.J.; Baranov, S.V.; Greenberg, H.K.; Porter, C.L.; Kristal, B.S. Dietary macronutrients modulate the fatty acyl composition of rat liver mitochondrial cardiolipins. J. Lipid Res. 2013, 54, 2623–2635.
64. Stanley, W.C.; Khairallah, R.J.; Dabkowski, E.R. Update on lipids and mitochondrial function: Impact of dietary n-3 polyunsaturated fatty acids. Curr. Opin. Clin. Nutr. Metab. Care. 2012, 15, 122–126.
65. Hulbert, A.; Turner, J.N.L.; Storlien, H.; Else, P.L. Dietary fats and membrane function: Implications for metabolism and disease. Biol. Rev. Camb. Philos. Soc. 2005, 1, 155–169.
66. Herbst, E.A.; Paglialunga, S.; Gerling, C.; Whitfield, J.; Mukai, K.; Chabowski, A.; Heigenhauser, G.J.; Spriet, L.L.; Holloway, G.P. Omega-3 supplementation alters mitochondrial membrane composition and respiration kinetics in human skeletal muscle. J. Physiol. 2014, 592, 1341–1352.
67. 2+ activation of PDH. Am. J. Physiol. 1999, 276, H149–H158.
68. Canuto, R.A.; Biocca, M.E.; Muzio, G.; Dianzani, M.U. Fatty acid composition of phospholipids in mitochondria and microsomes during diethylnitrosamine carcinogenesis in rat liver. Cell Biochem. Funct. 1989, 7, 11–19.
69. Olsson, J.M.; Eriksson, L.C.; Daliner, G. Lipid Compositions of Intracellular Membranes Isolated from Rat Liver Nodules in Wistar Rats. Cancer Res. 1991, 51, 3774–3780.
70. Hartz, J.W.; Morton, R.E.; Waite, M.M.; Morris, H.P. Correlation of fatty acyl composition of mitochondrial and microsomal phospholipid with growth rate of rat hepatomas. Lab. Investig. 1982, 46, 73–78.
71. Canuto, R.A.; Ferro, M.; Salvo, R.A.; Bassi, A.M.; Trombetta, A.; Maggiora, M.; Martinasso, G.; Lindahl, R.; Muzio, G. Increase in class 2 aldehyde dehydrogenase expression by arachidonic acid in rat hepatoma cells. Biochem. J. 2001, 357, 811–818.
72. Hoffmann, K.; Blaudszun, J.; Brunken, C.; Höpker, W.W.; Tauber, R.; Steinhart, H. Distribution of polyunsaturated fatty acids including conjugated linoleic acids in total and subcellular fractions from healthy and cancerous parts of human kidneys. Lipids 2005, 40, 309–315.
73. Wong, D.A.; Bassilian, S.; Lim, S.; Paul Lee, W.N. Coordination of peroxisomal beta-oxidation and fatty acid elongation in HepG2 cells. J. Biol. Chem. 2004, 279, 41302–41309.
74. Alfonso, P.; Núnez, A.; Madoz-Gurpide, J.; Lombardia, L.; Sánchez, L.; Casal, J.I. Proteomic expression analysis of colorectal cancer by two-dimensional differential gel electrophoresis. Proteomics 2005, 5, 2602–2611.
75. Capuano, F.; Guerrieri, F.; Papa, S. Oxidative phosphorylation enzymes innormal and neoplastic cell growth. J. Bioenerg. Biomembr. 1997, 29, 379–384.
76. Herrmann, P.C.; Gillespie, J.W.; Charboneau, L.; Bichsel, V.E.; Paweletz, C.P.; Calvert, V.S.; Kohn, E.C.; Emmert-Buck, M.R.; Liotta, L.A.; Petricoin, E.F., 3rd. Mitochondrial proteome: Altered cytochrome c oxidase subunit levels in prostate cancer. Proteomics 2003, 3, 1801–1810.
77. Buzzai, M.; Bauer, D.E.; Jones, R.G.; DeBerardinis, R.J.; Hatzivassiliou, G.; Elstrom, R.L.; Thompson, C.B. The glucose dependence of Akt-transformed cells can be reversed by pharmacologic activation of fatty acid beta-oxidation. Oncogene 2005, 24, 4165–4173.
78. Rodríguez-Enríquez, S.; Hernández-Esquivel, L.; Marín-Hernández, A.; El Hafidi, M.; Gallardo-Pérez, J.C.; Hernández-Reséndiz, I.; Rodríguez-Zavala, J.S.; Pacheco-Velázquez, S.C.; Moreno-Sánchez, R. Mitochondrial free fatty acid β-oxidation supports oxidative phosphorylation and proliferation in cancer cells. Int. J. Biochem. Cell Biol. 2015, 65, 209–221.
79. Kim, J.W.; Tchernyshyov, I.; Semenza, G.L.; Dang, C.V. HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 2006, 3, 177–185.
80. Gogvadze, V.; Zhivotovsky, B.; Orrenius, S. The Warburg effect and mitochondrial stability in cancer cells. Mol. Aspects Med. 2010, 31, 60–74.
81. Raza, H.; John, A.; Brown, E.M.; Benedict, S.; Kambal, A. Alterations in mitochondrial respiratory functions, redox metabolism and apoptosis by oxidant 4-hydroxynonenal and antioxidants curcumin and melatonin in PC12 cells. Toxicol. Appl. Pharmacol. 2008, 226, 161–168.
82. Huang, H.; Kozekov, I.D.; Kozekova, A.; Wang, H.; Lloyd, R.S.; Rizzo, C.J.; Stone, M.P. DNA cross-link induced by trans-4-hydroxynonenal. Environ. Mol. Mutagen. 2010, 51, 625–634.
83. Simonnet, H.; Alazard, N.; Pfeiffer, K.; Gallou, C.; Béroud, C.; Demont, J.; Bouvier, R.; Schägger, H.; Godinot, C. Low mitochondrial respiratory chain content correlates with tumor aggressiveness in renal cell carcinoma. Carcinogenesis 2002, 23, 759–768.
84. Barrera, G.; Pizzimenti, S.; Dianzani, M.U. Lipid peroxidation: Control of cell proliferation, cell differentiation and cell death. Mol. Aspects Med. 2008, 29, 1–8.
85. Esterbauer, H.; Schaur, R.J.; Zollner, H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic. Biol. Med. 1991, 11, 81–128.
86. Houtkooper, R.H.; Vaz, F.M. Cardiolipin, the heart of mitochondrial metabolism. Cell. Mol. Life Sci. 2008, 65, 2493–2506.
87. Yin, H.; Zhu, M. Free radical oxidation of cardiolipin: Chemical mechanisms, detection and implication in apoptosis, mitochondrial dysfunction and human diseases. Free Radic. Res. 2012, 46, 959–974.
88. iol. 2014, 2, 878–883.
89. Chen, J.J.; Yu, B.P. Alterations in mitochondrial membrane fluidity by lipid peroxidation products. Free Radic. Biol. Med. 1994, 17, 411–418.
90. Chatterjee, S.N.; Agarwal, S.; Kumarjana, A.; Bose, B. Membrane lipid peroxidation and its pathological consequences. Ind. J. Biochem. Biophys. 1988, 25, 25–31.
91. Borchman, D.; Lamba, O.P.; Salmassi, S.; Lou, M.; Yappert, M.C. The dual effect of oxidation on lipid bilayer structure. Lipids 1992, 27, 261–265.
92. Goldstein, R.M.; Weissmann, G. Effects of the generation of superoxide anion on permeability of liposomes. Biochem. Biophys. Res. Commun. 1977, 75, 604–609.
93. Anderson, E.J.; Katunga, L.A.; Willis, M.S. Mitochondria as a source and target of lipid peroxidation products in healthy and diseased heart. Clin. Exp. Pharmacol. Physiol. 2012, 39, 179–193.
94. Prasad, S.B.; Rosangkima, G.; Kharbangar, A. Structural and biochemical changes in mitochondria after cisplatin treatment of Dalton’s lymphoma-bearing mice. Mitochondrion 2010, 10, 38–45.
95. Gentile, F.; Pizzimenti, S.; Arcaro, A.; Pettazzoni, P.; Minelli, R.; D’Angelo, D.; Mamone, G.; Ferranti, P.; Toaldo, C.; Cetrangolo, G.; et al. Exposure of HL-60 human leukaemic cells to 4-hydroxynonenal promotes the formation of adduct(s) with alpha-enolase devoid of plasminogen binding activity. Biochem. J. 2009, 422, 285–294.
96. Zhao, Y.; Miriyala, S.; Miao, L.; Mitov, M.; Schnell, D.; Dhar, S.K.; Cai, J.; Klein, J.B.; Sultana, R.; Butterfield, D.A.; et al. Redox proteomic identification of HNE-bound mitochondrial proteins in cardiac tissues reveals a systemic effect on energy metabolism after doxorubicin treatment. Free Radic. Biol. Med. 2014, 72, 55–65.
97. Doorn, J.A.; Hurley, T.D.; Petersen, D.R. Inhibition of human mitochondrial aldehyde dehydrogenase by 4-Hydroxynon-2-enal and 4-Oxonon-2-enal. Chem. Res. Toxicol. 2006, 19, 102–110.
98. Ding, J.H.; Li, S.P.; Cao, H.X.; Wu, J.Z.; Gao, C.M.; Su, P.; Liu, Y.T.; Zhou, J.N.; Chang, J.; Yao, G.H. Polymorphisms of alcohol dehydrogenase-2 andaldehyde dehydrogenase-2 and esophageal cancer risk in Southeast Chinese males. World J. Gastroenterol. 2009, 15, 2395–2400.
99. Barrera, G. Oxidative stress and lipid peroxidation products in cancer progression and therapy. ISRN Oncol. 2012, 2012.
100. Awasthi, Y.C.; Ansari, G.A.; Awasthi, S. Regulation of 4-hydroxynonenal mediated signaling by glutathione S-transferases. Methods Enzymol. 2005, 401, 379–407.
101. Oberley, T.D.; Toyokuni, S.; Szweda, L.I. Localization of hydroxynonenal protein adducts in normal human kidney and selected human kidney cancers. Free Radic. Biol. Med. 1999, 27, 695–703.
102. Zhao, Y.; Xue, Y.; Oberley, T.D.; Kiningham, K.K.; Lin, S.M.; Yen, H.C.; Majima, H.; Hines, J.; St Clair, D. Overexpression of manganese superoxide dismutase suppresses tumor formation by modulation of activator protein-1 signaling in a multistage skin carcinogenesis model. Cancer Res. 2001, 61, 6082–6088.
103. Li, Y.P.; Tian, F.G.; Shi, P.C.; Guo, L.Y.; Wu, H.M.; Chen, R.Q.; Xue, J.M. 4-hydroxynonenal promotes growth and angiogenesis of breast cancer cells through HIF-1α stabilization. Asian Pac. J. Cancer Prev. 2014, 15, 10151–10156.
104. Zhang, H.; Du, Y.; Zhang, X.; Lu, J.; Holmgren, A. Glutaredoxin 2 reduces both thioredoxin 2 and thioredoxin 1 and protects cells from apoptosis induced by auranofin and 4-hydroxynonenal. Antioxid. Redox Signal. 2014, 21, 669–681.
105. Ji, C.; Amarnath, V.; Pietenpol, J.A.; Marnett, L.J. 4-hydroxynonenal induces apoptosis via caspase-3 activation and cytochrome c release. Chem. Res. Toxicol. 2001, 14, 1090–1096.
106. Haynes, R.L.; Brune, B.; Townsend, A.J. Apoptosis in RAW 264.7 cells exposed to 4-hydroxy-2-nonenal: Dependence on cytochrome C release but not p53 accumulation. Free Radic. Biol. Med. 2001, 30, 884–894.
107. Butterfield, D.A.; Reed, T.; Perluigi, M.; De Marco, C.; Coccia, R.; Cini, C.; Sultana, R. Elevated protein-bound levels of the lipid peroxidation product, 4-hydroxy-2-nonenal, in brain from persons with mild cognitive impairment. Neurosci. Lett. 2006, 397, 170–173.
108. Mangialasche, F.; Polidori, M.C.; Monastero, R.; Ercolani, S.; Camarda, C.; Cecchetti, R.; Mecucci, P. Biomarkers of oxidative and nitrosative damage in Alzheimer’s disease and mild cognitive impairment. Ageing Res. Rev. 2009, 8, 285–305.
109. Reed, T.; Perluigi, M.; Sultana, R.; Pierce, W.M.; Klein, J.B.; Turner, D.M.; Coccia, R.; Markesbery, W.R.; Butterfield, D.A. Redox proteomic identification of 4-hydroxy-2-nonenal modified brain proteins in amnestic mild cognitive impairment: Insight into the role of lipid peroxidation in the progression and pathogenesis of Alzheimer’s disease. Neurobiol. Dis. 2008, 30, 107–120.
110. in Res. 2009, 1274, 66–76.
111. Butterfield, D.A.; Bader Lange, M.L.; Sultana, R. Involvements of the lipid peroxidation product, HNE, in the pathogenesis and progression of Alzheimer’s disease. Biochim. Biophys. Acta 2010, 1801, 924–929.
112. Ruiperez, V.; Darios, F.; Davletov, B. Alpha-synuclein, lipids and Parkinson’s disease. Prog. Lipid Res. 2010, 49, 420–428.
113. Lee, J.; Kosaras, B.; del Signore, S.J.; Cormier, K.; McKe, A.; Ratan, R.R.; Kowall, N.W.; Ryu, H. Modulation of lipid peroxidation and mitochondrial function improves neuropathology in Huntington’s disease mice. Acta Neuropathol. 2011, 121, 487–498.
114. Shichiri, M.; Yoshida, Y.; Ishida, N.; Hagihara, Y.; Iwahashi, H.; Tamai, H.; Niki, E. Alpha-tocopgerol suppresses lipid peroxidation and behavioral and cognitive impairments in the Ts65Dn mouse model of Down syndrome. Free Radic. Biol. Med. 2011, 50, 1801–1811.
115. Berlett, B.S.; Stadtman, E.R. Protein oxidation in aging, disease, and oxidative stress. J. Biol. Chem. 1997, 272, 20313–20316.
116. Pamplona, R.; Dalfó, E.; Ayala, V.; Bellmunt, M.J.; Prat, J.; Ferrer, I.; Portero-Otín, M. Proteins in human brain cortex are modified by oxidation, glycoxidation, and lipoxidation. Effects of Alzheimer disease and identification of lipoxidation targets. J. Biol. Chem. 2005, 280, 21522–21530.
117. Grimsrud, P.A.; Xie, H.; Griffin, T.J.; Bernlohr, D.A. Oxidative stress and covalent modification of protein with bioactive aldehydes. J. Biol. Chem. 2008, 283, 21837–21841.
118. Keller, J.N.; Schmitt, F.A.; Scheff, S.W.; Ding, Q.; Chen, Q.; Butterfield, D.A.; Markesbery, W.R. Evidence of increased oxidative damage in subjects with mild cognitive impairment. Neurology 2005, 64, 1152–1156.
119. Butterfield, D.A.; Poon, H.F.; St Clair, D.; Keller, J.N.; Pierce, W.M.; Klein, J.B.; Markesbery, W.R. Redox proteomics identification of oxidatively modified hippocampal proteins in mild cognitive impairment: Insights into the development of Alzheimer’s disease. Neurobiol. Dis. 2006, 22, 223–232.
120. Sultana, R.; Perluigi, M.; Butterfield, D.A. Lipid peroxidation triggers neurodegeneration: A redox proteomics view into the Alzheimer disease brain. Free Radic. Biol. Med. 2013, 62, 157–169.
121. Perluigi, M.; Sultana, R.; Cenini, G.; di Domenico, F.; Memo, M.; Pierce, W.M.; Coccia, R.; Butterfield, D.A. Redox proteomics identification of 4-hydroxynonenal modified brain proteins in Alzheimer’s disease: Role of lipid peroxidation in Alzheimer’s disease pathogenesis. Proteomics Clin. Appl. 2009, 3, 682–693.
122. Martínez, A.; Portero-Otin, M.; Pamplona, R.; Ferrer, I. Protein targets of oxidative damage in human neurodegenerative diseases with abnormal protein aggregates. Brain Pathol. 2010, 20, 281–297.
123. Reed, T. Lipid peroxidation and neurodegenerative disease. Free Radic. Biol. Med. 2011, 51, 1302–1319.
124. Siegel, S.J.; Bieschke, J.; Powers, E.T.; Kelly, J.W. The oxidative stress metabolite 4-hydroxynonenal promotes Alzheimer protofibril formation. Biochemistry 2007, 46, 1503–1510.
125. Federico, A.; Cardaioli, E.; da Pozzo, P.; Formichi, P.; Gallus, G.N.; Radi, E. Mitochondria, oxidative stress and neurodegeneration. J. Neurol. Sci. 2012, 322, 254–262.
126. Bhat, A.H.; Dar, K.B.; Anees, S.; Zargar, M.A.; Masood, A.; Sofi, M.A.; Ganie, S.A. Oxidative stress, mitochondrial dysfunction and neurodegenerative diseases; a mechanistic insight. Biomed. Pharmacother. 2015, 74, 101–110.
127. Online Mendelian Inheritance in Man (OMIM) database. Availalbe online: http://www.ncbi.nlm.nih.gov/ omim (accessed on 17 February 2016).
128. Terni, B.; Boada, J.; Portero-Otín, M.; Pamplona, R.; Ferrer, I. Mitochondrial ATP-synthase in the entorhinal cortex is a target of oxidative stress at stages I/II of Alzheimer’s disease pathology. Brain Pathol. 2010, 20, 222–233.
129. Sorolla, M.A.; Reverter-Branchat, G.; Tamarit, J.; Ferrer, I.; Ros, J.; Cabiscol, E. Proteomic and oxidative stress analysis in human brain samples of Huntington disease. Free Radic. Biol. Med. 2008, 45, 667–678.
130. Sorolla, M.A.; Rodríguez-Colman, M.J.; Tamarit, J.; Ortega, Z.; Lucas, J.J.; Ferrer, I.; Ros, J.; Cabiscol, E. Protein oxidation in Huntington disease affects energy production and vitamin B6 metabolism. Free Radic. Biol. Med. 2010, 49, 612–621.
131. Choi, J.; Sullards, M.C.; Olzmann, J.A.; Rees, H.D.; Weintraub, S.T.; Bostwick, D.E.; Gearing, M.; Levey, A.I.; Chin, L.S.; Li, L. Oxidative damage of DJ-1 is linked to sporadic Parkinson and Alzheimer diseases. J. Biol. Chem. 2006, 281, 10816–10824.
132. Keeney, P.M.; Xie, J.; Capaldi, R.A.; Bennett, J.P. Parkinson’s disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled. J. Neurosci. 2006, 26, 5256–5264.
133. Choi, J.; Rees, H.D.; Weintraub, S.T.; Levey, A.I.; Chin, L.-S.; Li, L. Oxidative modifications and aggregation of Cu,Zn-superoxide dismutase associated with Alzheimer and Parkinson diseases. J. Biol. Chem. 2005, 280, 11648–11655.
134. Cabiscol, E.; Ros, J. Oxidative damage to proteins: Structural modifications and consequences in cell function. In Redox Proteomics: From Protein Modifications to Cellular Dysfunctions and Diseases; Dalle-Donne, I., Scaloni, A., Butterfield, D.A., Eds.; Wiley: Hoboken, NJ, USA, 2006; pp. 399–472.
135. Chen, X.J.; Wang, X.; Kaufman, B.A.; Butow, R.A. Aconitase couples metabolic regulation to mitochondrial DNA maintenance. Science 2005, 307, 714–717.
136. Schagger, H.; Ohm, T.G. Human diseases with defects in oxidative phosphorylation. 2. F1F0 ATP-synthase defects in Alzheimer disease revealed by blue native polyacrylamide gel electrophoresis. Eur. J. Biochem. 1995, 227, 916–921.
137. Rhein, V.; Eckert, A. Effects of Alzheimer’s amyloid-beta and tau protein on mitochondrial function—Role of glucose metabolism and insulin signalling. Arch. Physiol. Biochem. 2007, 113, 131–141.
138. Sultana, R.; Poon, H.F.; Cai, J.; Pierce, W.M.; Merchant, M.; Klein, J.B.; Markesbery, W.R.; Butterfield, D.A. Identification of nitrated proteins in Alzheimer’s disease brain using a redox proteomics approach. Neurobiol. Dis. 2006, 22, 76–87.
139. Mattiazzi, M.; Vijayvergiya, C.; Gajewski, C.D.; DeVivo, D.C.; Lenaz, G.; Wiedmann, M.; Manfredi, G. The mtDNA T8993G (NARP) mutation results in an impairment of oxidative phosphorylation that can be improved by antioxidants. Hum. Molec. Genet. 2007, 13, 869–879.
140. Hansen, J.J.; Durr, A.; Cournu-Rebeix, I.; Georgopoulos, C.; Ang, D.; Nielsen, M.N.; Davoine, C.S.; Brice, A.; Fontaine, B.; Gregersen, N.; et al. Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60. Am. J. Hum. Genet. 2002, 70, 1328–1332.
141. Tabrizi, S.J.; Cleeter, M.W.; Xuereb, J.; Taanman, J.W.; Cooper, J.M.; Schapira, A.H. Biochemical abnormalities and excitotoxicity in Huntington’s disease brain. Ann. Neurol. 1999, 45, 25–32.
142. Solans, A.; Zambrano, A.; Rodríguez, M.; Barrientos, A. Cytotoxicity of a mutant huntingtin fragment in yeast involves early alterations in mitochondrial OXPHOS complexes II and III. Hum. Mol. Genet. 2006, 15, 3063–3081.
143. Miyake, N.; Yano, S.; Sakai, C.; Hatakeyama, H.; Matsushima, Y.; Shiina, M.; Watanabe, Y.; Bartley, J.; Abdenut, J.E.; Wang, R.Y.; et al. Mitochondrial complex III deficiency caused by a homozygous UQCRC2 mutation presenting with neonatal-onset recurrent metabolic decompensation. Hum. Mutat. 2013, 34, 446–452.
144. Richarme, G.; Mihoub, M.; Dairou, J.; Bui, L.C.; Leger, T.; Lamouri, A. Parkinsonism-associated protein DJ-1/Park7 is a major protein deglycase that repairs methylglyoxal- and glyoxal-glycated cysteine, arginine, and lysine residues. J. Biol. Chem. 2015, 290, 1885–1897.
145. 2 -induced cell death. Free Radic. Res. 2006, 40, 155–165.
146. Björkblom, B.; Adilbayeva, A.; Maple-Grødem, J.; Piston, D.; Ökvist, M.; Xu, X.M.; Brede, C.; Larsen, J.P.; Møller, S.G. Parkinson disease protein DJ-1 binds metals and protects against metal-induced cytotoxicity. J. Biol. Chem. 2013, 288, 22809–22820.
147. Xiong, H.; Wang, D.; Chen, L.; Choo, Y.S.; Ma, H.; Tang, C.; Xia, K.; Jiang, W.; Ronai, Z.; Zhuang, X.; et al. Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting unfolded protein degradation. J. Clin. Investig. 2009, 119, 650–660.
148. Tang, B.; Xiong, H.; Sun, P.; Zhang, Y.; Wang, D.; Hu, Z.; Zhu, Z.; Ma, H.; Pan, Q.; Xia, J.H.; et al. Association of PINK1 and DJ-1 confers digenic inheritance of early-onset Parkinson’s disease. Hum. Mol. Genet. 2006, 15, 1816–1825.
149. Junn, E.; Jang, W.H.; Zhao, X.; Jeong, B.S.; Mouradian, M.M. Mitochondrial localization of DJ-1 leads to enhanced neuroprotection. J. Neurosci. Res. 2009, 87, 123–129.
150. Rizzu, P.; Hinkle, D.A.; Zhukareva, V.; Bonifati, V.; Severijnen, L.A.; Martinez, D.; Ravid, R.; Kamphorst, W.; Eberwine, J.H.; Lee, V.M.; et al. DJ-1 colocalizes with tau inclusions: A link between Parkinsonism and dementia. Ann. Neurol. 2004, 55, 113–118.
151. Shults, C.W. Mitochondrial dysfunction and possible treatments in Parkinson’s disease—A review. Mitochondrion 2004, 4, 641–648.
152. Schumacker, P.T. Reactive oxygen species in cancer cells: Live by the sword, die by the sword. Cancer Cell 2006, 10, 175–176.
153. Fruehauf, J.P.; Meyskens, F.L., Jr. Reactive oxygen species: A breath of life or death? Clin. Cancer Res. 2007, 13, 789–794.
154. Kardeh, S.; Ashkani-Esfahani, S.; Alizadeh, A.M. Paradoxical action of reactive oxygen species in creation and therapy of cancer. Eur. J. Pharmacol. 2014, 735, 150–168.
155. Cojocneanu Petric, R.; Braicu, C.; Raduly, L.; Zanoaga, O.; Dragos, N.; Monroig, P.; Dumitrascu, D.; Berindan-Neagoe, I. Phytochemicals modulate carcinogenic signaling pathways in breast and hormone-related cancers. Onco Targets Ther. 2015, 8, 2053–2066.
156. Galasko, D.R.; Peskind, E.; Clark, C.M.; Quinn, J.F.; Ringman, J.M.; Jicha, G.A.; Cotman, C.; Cottrell, B.; Montine, T.J.; Thomas, R.G.; et al. Alzheimer’s Disease Cooperative Study. Antioxidants for Alzheimer disease: A randomized clinical trial with cerebrospinal fluid biomarker measures. Arch. Neurol. 2012, 69, 836–841.
157. Gandhi, S.; Abramov, A.Y. Mechanism of oxidative stress in neurodegeneration. Oxid. Med. Cell Longev. 2012, 2012.