Mitochondrial reactive oxygen species: Do they extend or shorten animal lifespan?

Biochimica et Biophysica Acta - Bioenergetics

Volumn 1857, Issue 8, 2016, Pages 1116-1126

  Sanz, Alberto ^a  

^a NEWCASTLE UNIVERSITY   (United Kingdom)

Author keywords

Aging; Caenorhabditis elegans; Drosophila melanogaster; Electron transport chain; Hydrogen peroxide; Mitochondria; Mus musculus; Reactive oxygen species; Superoxide

Indexed keywords

REACTIVE OXYGEN METABOLITE; BACTERIAL PROTEIN; GREEN FLUORESCENT PROTEIN; HYDROGEN PEROXIDE; MULTIENZYME COMPLEX; PHOTOPROTEIN; SUPEROXIDE; YELLOW FLUORESCENT PROTEIN, BACTERIA;

AGING; DISEASES; HEALTH; HUMAN; IN VITRO STUDY; IN VIVO STUDY; LIFESPAN; LONGEVITY; MEASUREMENT; MITOCHONDRION; NONHUMAN; PRIORITY JOURNAL; REVIEW; ANIMAL; CAENORHABDITIS ELEGANS; DROSOPHILA MELANOGASTER; ELECTRON TRANSPORT; GENE EXPRESSION; GENETICS; METABOLISM; MOUSE; REPORTER GENE;

AGING; ANIMALS; BACTERIAL PROTEINS; CAENORHABDITIS ELEGANS; DROSOPHILA MELANOGASTER; ELECTRON TRANSPORT; ELECTRON TRANSPORT CHAIN COMPLEX PROTEINS; GENE EXPRESSION; GENES, REPORTER; GREEN FLUORESCENT PROTEINS; HYDROGEN PEROXIDE; LONGEVITY; LUMINESCENT PROTEINS; MICE; MITOCHONDRIA; SUPEROXIDES;

EID: 84961839456     PISSN: 00052728     EISSN: 18792650     Source Type: Journal    
DOI: 10.1016/j.bbabio.2016.03.018     Document Type: Review

References (163)

1. [1] Harman, D., Aging: a theory based on free radical and radiation chemistry. J. Gerontol. 11 (1956), 298–300.
2. [2] Harman, D., The biologic clock: the mitochondria?. J. Am. Geriatr. Soc. 20 (1972), 145–147.
3. [3] Forster, M.J., Dubey, A., Dawson, K.M., Stutts, W.A., Lal, H., Sohal, R.S., Age-related losses of cognitive function and motor skills in mice are associated with oxidative protein damage in the brain. Proc. Natl. Acad. Sci. U. S. A. 93 (1996), 4765–4769.
4. [4] Choksi, K.B., Nuss, J.E., Deford, J.H., Papaconstantinou, J., Age-related alterations in oxidatively damaged proteins of mouse skeletal muscle mitochondrial electron transport chain complexes. Free Radic. Biol. Med. 45 (2008), 826–838.
5. [5] Gan, W., Nie, B., Shi, F., Xu, X.M., Qian, J.C., Takagi, Y., Hayakawa, H., Sekiguchi, M., Cai, J.P., Age-dependent increases in the oxidative damage of DNA, RNA, and their metabolites in normal and senescence-accelerated mice analyzed by LC–MS/MS: urinary 8-oxoguanosine as a novel biomarker of aging. Free Radic. Biol. Med. 52 (2012), 1700–1707.
6. [6] Toroser, D., Orr, W.C., Sohal, R.S., Carbonylation of mitochondrial proteins in Drosophila melanogaster during aging. Biochem. Biophys. Res. Commun. 363 (2007), 418–424.
7. [7] Ku, H.H., Sohal, R.S., Comparison of mitochondrial pro-oxidant generation and anti-oxidant defenses between rat and pigeon: possible basis of variation in longevity and metabolic potential. Mech. Ageing Dev. 72 (1993), 67–76.
8. 2 consumption can explain the simultaneous presence of high longevity and high aerobic metabolic rate in birds. Free Radic. Res. 21 (1994), 317–327.
9. [9] Lambert, A.J., Boysen, H.M., Buckingham, J.A., Yang, T., Podlutsky, A., Austad, S.N., Kunz, T.H., Buffenstein, R., Brand, M.D., Low rates of hydrogen peroxide production by isolated heart mitochondria associate with long maximum lifespan in vertebrate homeotherms. Aging Cell 6 (2007), 607–618.
10. [10] Qiu, X., Brown, K., Hirschey, M.D., Verdin, E., Chen, D., Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. Cell Metab. 12 (2010), 662–667.
11. [11] Gredilla, R., Sanz, A., Lopez-Torres, M., Barja, G., Caloric restriction decreases mitochondrial free radical generation at complex I and lowers oxidative damage to mitochondrial DNA in the rat heart. FASEB J. 15 (2001), 1589–1591.
12. [12] Sanz, A., Caro, P., Ayala, V., Portero-Otin, M., Pamplona, R., Barja, G., Methionine restriction decreases mitochondrial oxygen radical generation and leak as well as oxidative damage to mitochondrial DNA and proteins. FASEB J. 20 (2006), 1064–1073.
13. [13] Zhang, J., Perry, G., Smith, M.A., Robertson, D., Olson, S.J., Graham, D.G., Montine, T.J., Parkinson's disease is associated with oxidative damage to cytoplasmic DNA and RNA in substantia nigra neurons. Am. J. Pathol. 154 (1999), 1423–1429.
14. 2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. J. Clin. Invest. 119 (2009), 573–581.
15. [15] Szatrowski, T.P., Nathan, C.F., Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res. 51 (1991), 794–798.
16. [16] Van Remmen, H., Ikeno, Y., Hamilton, M., Pahlavani, M., Wolf, N., Thorpe, S.R., Alderson, N.L., Baynes, J.W., Epstein, C.J., Huang, T.T., Nelson, J., Strong, R., Richardson, A., Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. Physiol. Genomics 16 (2003), 29–37.
17. [17] Yang, W., Hekimi, S., A mitochondrial superoxide signal triggers increased longevity in Caenorhabditis elegans. PLoS Biol., 8, 2010, e1000556.
18. [18] Sanz, A., Fernandez-Ayala, D.J., Stefanatos, R.K., Jacobs, H.T., Mitochondrial ROS production correlates with, but does not directly regulate lifespan in Drosophila. Aging (Albany NY) 2 (2010), 200–223.
19. [19] Sanz, A., Pamplona, R., Barja, G., Is the mitochondrial free radical theory of aging intact?. Antioxid. Redox Signal. 8 (2006), 582–599.
20. [20] Muller, F.L., Lustgarten, M.S., Jang, Y., Richardson, A., Van Remmen, H., Trends in oxidative aging theories. Free Radic. Biol. Med. 43 (2007), 477–503.
21. [21] Van Raamsdonk, J.M., Hekimi, S., Superoxide dismutase is dispensable for normal animal lifespan. Proc. Natl. Acad. Sci. U. S. A. 109 (2012), 5785–5790.
22. [22] Richardson, J.R., Quan, Y., Sherer, T.B., Greenamyre, J.T., Miller, G.W., Paraquat neurotoxicity is distinct from that of MPTP and rotenone. Toxicol. Sci. 88 (2005), 193–201.
23. [23] Yang, W., Hekimi, S., Two modes of mitochondrial dysfunction lead independently to lifespan extension in Caenorhabditis elegans. Aging Cell 9 (2010), 433–447.
24. [24] Owusu-Ansah, E., Song, W., Perrimon, N., Muscle mitohormesis promotes longevity via systemic repression of insulin signaling. Cell 155 (2013), 699–712.
25. [25] Ristow, M., Zarse, K., How increased oxidative stress promotes longevity and metabolic health: the concept of mitochondrial hormesis (mitohormesis). Exp. Gerontol. 45 (2010), 410–418.
26. [26] Weyemi, U., Lagente-Chevallier, O., Boufraqech, M., Prenois, F., Courtin, F., Caillou, B., Talbot, M., Dardalhon, M., Al Ghuzlan, A., Bidart, J.M., Schlumberger, M., Dupuy, C., ROS-generating NADPH oxidase NOX4 is a critical mediator in oncogenic H-Ras-induced DNA damage and subsequent senescence. Oncogene 31 (2012), 1117–1129.
27. [27] Delmaghani, S., Defourny, J., Aghaie, A., Beurg, M., Dulon, D., Thelen, N., Perfettini, I., Zelles, T., Aller, M., Meyer, A., Emptoz, A., Giraudet, F., Leibovici, M., Dartevelle, S., Soubigou, G., Thiry, M., Vizi, E.S., Safieddine, S., Hardelin, J.P., Avan, P., Petit, C., Hypervulnerability to sound exposure through impaired adaptive proliferation of peroxisomes. Cell 163 (2015), 894–906.
28. [28] Schaar, C.E., Dues, D.J., Spielbauer, K.K., Machiela, E., Cooper, J.F., Senchuk, M., Hekimi, S., Van Raamsdonk, J.M., Mitochondrial and cytoplasmic ROS have opposing effects on lifespan. PLoS Genet., 11, 2015, e1004972.
29. [29] Lackner, L.L., Nunnari, J.M., The molecular mechanism and cellular functions of mitochondrial division. Biochim. Biophys. Acta 1792 (2009), 1138–1144.
30. [30] West, A.P., Brodsky, I.E., Rahner, C., Woo, D.K., Erdjument-Bromage, H., Tempst, P., Walsh, M.C., Choi, Y., Shadel, G.S., Ghosh, S., TLR signalling augments macrophage bactericidal activity through mitochondrial ROS. Nature 472 (2011), 476–480.
31. [31] Owusu-Ansah, E., Banerjee, U., Reactive oxygen species prime Drosophila haematopoietic progenitors for differentiation. Nature 461 (2009), 537–541.
32. [32] Sakai, K., Matsumoto, K., Nishikawa, T., Suefuji, M., Nakamaru, K., Hirashima, Y., Kawashima, J., Shirotani, T., Ichinose, K., Brownlee, M., Araki, E., Mitochondrial reactive oxygen species reduce insulin secretion by pancreatic beta-cells. Biochem. Biophys. Res. Commun. 300 (2003), 216–222.
33. [33] Lightowlers, R.N., Taylor, R.W., Turnbull, D.M., Mutations causing mitochondrial disease: what is new and what challenges remain?. Science 349 (2015), 1494–1499.
34. [34] Boveris, A., Oshino, N., Chance, B., The cellular production of hydrogen peroxide. Biochem. J. 128 (1972), 617–630.
35. [35] Lopez-Otin, C., Blasco, M.A., Partridge, L., Serrano, M., Kroemer, G., The hallmarks of aging. Cell 153 (2013), 1194–1217.
36. [36] Tanner, C.M., Kamel, F., Ross, G.W., Hoppin, J.A., Goldman, S.M., Korell, M., Marras, C., Bhudhikanok, G.S., Kasten, M., Chade, A.R., Comyns, K., Richards, M.B., Meng, C., Priestley, B., Fernandez, H.H., Cambi, F., Umbach, D.M., Blair, A., Sandler, D.P., Langston, J.W., Rotenone, paraquat, and Parkinson's disease. Environ. Health Perspect. 119 (2011), 866–872.
37. [37] Owen, M.R., Doran, E., Halestrap, A.P., Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem. J. 348:Pt 3 (2000), 607–614.
38. [38] Wang, Y., Oxer, D., Hekimi, S., Mitochondrial function and lifespan of mice with controlled ubiquinone biosynthesis. Nat. Commun., 6, 2015, 6393.
39. [39] Kujoth, G.C., Hiona, A., Pugh, T.D., Someya, S., Panzer, K., Wohlgemuth, S.E., Hofer, T., Seo, A.Y., Sullivan, R., Jobling, W.A., Morrow, J.D., Van Remmen, H., Sedivy, J.M., Yamasoba, T., Tanokura, M., Weindruch, R., Leeuwenburgh, C., Prolla, T.A., Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 309 (2005), 481–484.
40. [40] Hiona, A., Sanz, A., Kujoth, G.C., Pamplona, R., Seo, A.Y., Hofer, T., Someya, S., Miyakawa, T., Nakayama, C., Samhan-Arias, A.K., Servais, S., Barger, J.L., Portero-Otin, M., Tanokura, M., Prolla, T.A., Leeuwenburgh, C., Mitochondrial DNA mutations induce mitochondrial dysfunction, apoptosis and sarcopenia in skeletal muscle of mitochondrial DNA mutator mice. PLoS One, 5, 2010, e11468.
41. [41] Kalyanaraman, B., Darley-Usmar, V., Davies, K.J., Dennery, P.A., Forman, H.J., Grisham, M.B., Mann, G.E., Moore, K., Roberts, L.J. 2nd, Ischiropoulos, H., Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations. Free Radic. Biol. Med. 52 (2012), 1–6.
42. [42] Brown, G.C., Borutaite, V., There is no evidence that mitochondria are the main source of reactive oxygen species in mammalian cells. Mitochondrion 12 (2012), 1–4.
43. [43] Clancy, R.M., Leszczynska-Piziak, J., Abramson, S.B., Nitric oxide, an endothelial cell relaxation factor, inhibits neutrophil superoxide anion production via a direct action on the NADPH oxidase. J. Clin. Invest. 90 (1992), 1116–1121.
44. [44] Droge, W., Free radicals in the physiological control of cell function. Physiol. Rev. 82 (2002), 47–95.
45. [45] Gutteridge, J.M., The role of superoxide and hydroxyl radicals in phospholipid peroxidation catalysed by iron salts. FEBS Lett. 150 (1982), 454–458.
46. [46] Esposito, G., Vos, M., Vilain, S., Swerts, J., De Sousa Valadas, J., Van Meensel, S., Schaap, O., Verstreken, P., Aconitase causes iron toxicity in Drosophila pink1 mutants. PLoS Genet., 9, 2013, e1003478.
47. [47] Li, Y., Huang, T.T., Carlson, E.J., Melov, S., Ursell, P.C., Olson, J.L., Noble, L.J., Yoshimura, M.P., Berger, C., Chan, P.H., Wallace, D.C., Epstein, C.J., Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Nat. Genet. 11 (1995), 376–381.
48. [48] Chevion, M., A site-specific mechanism for free radical induced biological damage: the essential role of redox-active transition metals. Free Radic. Biol. Med. 5 (1988), 27–37.
49. [49] Forman, H.J., Maiorino, M., Ursini, F., Signaling functions of reactive oxygen species. Biochemistry 49 (2010), 835–842.
50. 2-induced signaling. Methods Enzymol. 527 (2013), 41–63.
51. [51] De Haes, W., Frooninckx, L., Van Assche, R., Smolders, A., Depuydt, G., Billen, J., Braeckman, B.P., Schoofs, L., Temmerman, L., Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2. Proc. Natl. Acad. Sci. U. S. A. 111 (2014), E2501–E2509.
52. [52] Bravo, R., Vicencio, J.M., Parra, V., Troncoso, R., Munoz, J.P., Bui, M., Quiroga, C., Rodriguez, A.E., Verdejo, H.E., Ferreira, J., Iglewski, M., Chiong, M., Simmen, T., Zorzano, A., Hill, J.A., Rothermel, B.A., Szabadkai, G., Lavandero, S., Increased ER-mitochondrial coupling promotes mitochondrial respiration and bioenergetics during early phases of ER stress. J. Cell Sci. 124 (2011), 2143–2152.
53. 2 and cumene hydroperoxide treatment on heart mitochondria. J. Bioenerg. Biomembr. 38 (2006), 121–127.
54. [54] Sanz, A., Stefanatos, R., McIlroy, G., Production of reactive oxygen species by the mitochondrial electron transport chain in Drosophila melanogaster. J. Bioenerg. Biomembr. 42 (2010), 135–142.
55. [55] Esterhazy, D., King, M.S., Yakovlev, G., Hirst, J., Production of reactive oxygen species by complex I (NADH:ubiquinone oxidoreductase) from Escherichia coli and comparison to the enzyme from mitochondria. Biochemistry 47 (2008), 3964–3971.
56. [56] Muller, F.L., Liu, Y., Van Remmen, H., Complex III releases superoxide to both sides of the inner mitochondrial membrane. J. Biol. Chem. 279 (2004), 49064–49073.
57. [57] Quinlan, C.L., Goncalves, R.L., Hey-Mogensen, M., Yadava, N., Bunik, V.I., Brand, M.D., The 2-oxoacid dehydrogenase complexes in mitochondria can produce superoxide/hydrogen peroxide at much higher rates than complex I. J. Biol. Chem. 289 (2014), 8312–8325.
58. [58] Treberg, J.R., Quinlan, C.L., Brand, M.D., Hydrogen peroxide efflux from muscle mitochondria underestimates matrix superoxide production—a correction using glutathione depletion. FEBS J. 277 (2010), 2766–2778.
59. [59] Stefanatos, R., Sanz, A., Mitochondrial complex I: a central regulator of the aging process. Cell Cycle 10 (2011), 1528–1532.
60. [60] Bevilacqua, L., Ramsey, J.J., Hagopian, K., Weindruch, R., Harper, M.E., Effects of short- and medium-term calorie restriction on muscle mitochondrial proton leak and reactive oxygen species production. Am. J. Physiol. Endocrinol. Metab. 286 (2004), E852–E861.
61. [61] Quinlan, C.L., Orr, A.L., Perevoshchikova, I.V., Treberg, J.R., Ackrell, B.A., Brand, M.D., Mitochondrial complex II can generate reactive oxygen species at high rates in both the forward and reverse reactions. J. Biol. Chem. 287 (2012), 27255–27264.
62. [62] Chouchani, E.T., Pell, V.R., Gaude, E., Aksentijevic, D., Sundier, S.Y., Robb, E.L., Logan, A., Nadtochiy, S.M., Ord, E.N., Smith, A.C., Eyassu, F., Shirley, R., Hu, C.H., Dare, A.J., James, A.M., Rogatti, S., Hartley, R.C., Eaton, S., Costa, A.S., Brookes, P.S., Davidson, S.M., Duchen, M.R., Saeb-Parsy, K., Shattock, M.J., Robinson, A.J., Work, L.M., Frezza, C., Krieg, T., Murphy, M.P., Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature 515 (2014), 431–435.
63. [63] Murphy, M.P., How mitochondria produce reactive oxygen species. Biochem. J. 417 (2009), 1–13.
64. [64] Beltran, B., Quintero, M., Garcia-Zaragoza, E., O'Connor, E., Esplugues, J.V., Moncada, S., Inhibition of mitochondrial respiration by endogenous nitric oxide: a critical step in Fas signaling. Proc. Natl. Acad. Sci. U. S. A. 99 (2002), 8892–8897.
65. [65] Taylor, C.T., Moncada, S., Nitric oxide, cytochrome C oxidase, and the cellular response to hypoxia. Arterioscler. Thromb. Vasc. Biol. 30 (2010), 643–647.
66. [66] Busuttil, R.A., Rubio, M., Dolle, M.E., Campisi, J., Vijg, J., Oxygen accelerates the accumulation of mutations during the senescence and immortalization of murine cells in culture. Aging Cell 2 (2003), 287–294.
67. [67] MacVicar, T.D., Lane, J.D., Impaired OMA1-dependent cleavage of OPA1 and reduced DRP1 fission activity combine to prevent mitophagy in cells that are dependent on oxidative phosphorylation. J. Cell Sci. 127 (2014), 2313–2325.
68. [68] Narendra, D., Tanaka, A., Suen, D.F., Youle, R.J., Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J. Cell Biol. 183 (2008), 795–803.
69. [69] Kubli, D.A., Zhang, X., Lee, Y., Hanna, R.A., Quinsay, M.N., Nguyen, C.K., Jimenez, R., Petrosyan, S., Murphy, A.N., Gustafsson, A.B., Parkin protein deficiency exacerbates cardiac injury and reduces survival following myocardial infarction. J. Biol. Chem. 288 (2013), 915–926.
70. [70] Perez, F.A., Palmiter, R.D., Parkin-deficient mice are not a robust model of parkinsonism. Proc. Natl. Acad. Sci. U. S. A. 102 (2005), 2174–2179.
71. [71] Wiley, C.D., Velarde, M.C., Lecot, P., Liu, S., Sarnoski, E.A., Freund, A., Shirakawa, K., Lim, H.W., Davis, S.S., Ramanathan, A., Gerencser, A.A., Verdin, E., Campisi, J., Mitochondrial dysfunction induces senescence with a distinct secretory phenotype. Cell Metab., 2015.
72. [72] Joselin, A.P., Hewitt, S.J., Callaghan, S.M., Kim, R.H., Chung, Y.H., Mak, T.W., Shen, J., Slack, R.S., Park, D.S., ROS-dependent regulation of Parkin and DJ-1 localization during oxidative stress in neurons. Hum. Mol. Genet. 21 (2012), 4888–4903.
73. [73] Passos, J.F., Saretzki, G., Ahmed, S., Nelson, G., Richter, T., Peters, H., Wappler, I., Birket, M.J., Harold, G., Schaeuble, K., Birch-Machin, M.A., Kirkwood, T.B., von Zglinicki, T., Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence. PLoS Biol., 5, 2007, e110.
74. [74] Rodenburg, R.J., Biochemical diagnosis of mitochondrial disorders. J. Inherit. Metab. Dis. 34 (2011), 283–292.
75. [75] Hamalainen, R.H., Manninen, T., Koivumaki, H., Kislin, M., Otonkoski, T., Suomalainen, A., Tissue- and cell-type-specific manifestations of heteroplasmic mtDNA 3243A > G mutation in human induced pluripotent stem cell-derived disease model. Proc. Natl. Acad. Sci. U. S. A. 110 (2013), E3622–E3630.
76. [76] Wang, X., Fang, H., Huang, Z., Shang, W., Hou, T., Cheng, A., Cheng, H., Imaging ROS signaling in cells and animals. J. Mol. Med. (Berl.) 91 (2013), 917–927.
77. [77] Wang, W., Fang, H., Groom, L., Cheng, A., Zhang, W., Liu, J., Wang, X., Li, K., Han, P., Zheng, M., Yin, J., Wang, W., Mattson, M.P., Kao, J.P., Lakatta, E.G., Sheu, S.S., Ouyang, K., Chen, J., Dirksen, R.T., Cheng, H., Superoxide flashes in single mitochondria. Cell 134 (2008), 279–290.
78. [78] Schwarzlander, M., Wagner, S., Ermakova, Y.G., Belousov, V.V., Radi, R., Beckman, J.S., Buettner, G.R., Demaurex, N., Duchen, M.R., Forman, H.J., Fricker, M.D., Gems, D., Halestrap, A.P., Halliwell, B., Jakob, U., Johnston, I.G., Jones, N.S., Logan, D.C., Morgan, B., Muller, F.L., Nicholls, D.G., Remington, S.J., Schumacker, P.T., Winterbourn, C.C., Sweetlove, L.J., Meyer, A.J., Dick, T.P., Murphy, M.P., The ‘mitoflash’ probe cpYFP does not respond to superoxide. Nature 514 (2014), E12–E14.
79. [79] Shen, E.Z., Song, C.Q., Lin, Y., Zhang, W.H., Su, P.F., Liu, W.Y., Zhang, P., Xu, J., Lin, N., Zhan, C., Wang, X., Shyr, Y., Cheng, H., Dong, M.Q., Mitoflash frequency in early adulthood predicts lifespan in Caenorhabditis elegans. Nature 508 (2014), 128–132.
80. [80] Markvicheva, K.N., Bogdanova, E.A., Staroverov, D.B., Lukyanov, S., Belousov, V.V., Imaging of intracellular hydrogen peroxide production with HyPer upon stimulation of HeLa cells with epidermal growth factor. Methods Mol. Biol. 476 (2008), 79–86.
81. [81] Knoefler, D., Thamsen, M., Koniczek, M., Niemuth, N.J., Diederich, A.K., Jakob, U., Quantitative in vivo redox sensors uncover oxidative stress as an early event in life. Mol. Cell 47 (2012), 767–776.
82. [82] Meyer, A.J., Brach, T., Marty, L., Kreye, S., Rouhier, N., Jacquot, J.P., Hell, R., Redox-sensitive GFP in Arabidopsis thaliana is a quantitative biosensor for the redox potential of the cellular glutathione redox buffer. Plant J. 52 (2007), 973–986.
83. 2-scavenging peroxidases. J. Biol. Chem. 284 (2009), 31532–31540.
84. [84] Albrecht, S.C., Barata, A.G., Grosshans, J., Teleman, A.A., Dick, T.P., In vivo mapping of hydrogen peroxide and oxidized glutathione reveals chemical and regional specificity of redox homeostasis. Cell Metab. 14 (2011), 819–829.
85. 2 within living Drosophila during aging using a ratiometric mass spectrometry probe targeted to the mitochondrial matrix. Cell Metab. 13 (2011), 340–350.
86. [86] Zhao, H., Kalivendi, S., Zhang, H., Joseph, J., Nithipatikom, K., Vasquez-Vivar, J., Kalyanaraman, B., Superoxide reacts with hydroethidine but forms a fluorescent product that is distinctly different from ethidium: potential implications in intracellular fluorescence detection of superoxide. Free Radic. Biol. Med. 34 (2003), 1359–1368.
87. [87] Magwere, T., West, M., Riyahi, K., Murphy, M.P., Smith, R.A., Partridge, L., The effects of exogenous antioxidants on lifespan and oxidative stress resistance in Drosophila melanogaster. Mech. Ageing Dev. 127 (2006), 356–370.
88. [88] Bleier, L., Wittig, I., Heide, H., Steger, M., Brandt, U., Drose, S., Generator-specific targets of mitochondrial reactive oxygen species. Free Radic. Biol. Med. 78 (2015), 1–10.
89. [89] Narayanasamy, S.K., Simpson, D.C., Martin, I., Grotewiel, M., Gronert, S., Paraquat exposure and Sod2 knockdown have dissimilar impacts on the Drosophila melanogaster carbonylated protein proteome. Proteomics 14 (2014), 2566–2577.
90. [90] Andres-Mateos, E., Perier, C., Zhang, L., Blanchard-Fillion, B., Greco, T.M., Thomas, B., Ko, H.S., Sasaki, M., Ischiropoulos, H., Przedborski, S., Dawson, T.M., Dawson, V.L., DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase. Proc. Natl. Acad. Sci. U. S. A. 104 (2007), 14807–14812.
91. [91] Bonifati, V., Rizzu, P., van Baren, M.J., Schaap, O., Breedveld, G.J., Krieger, E., Dekker, M.C., Squitieri, F., Ibanez, P., Joosse, M., van Dongen, J.W., Vanacore, N., van Swieten, J.C., Brice, A., Meco, G., van Duijn, C.M., Oostra, B.A., Heutink, P., Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299 (2003), 256–259.
92. [92] Copeland, J.M., Cho, J., Lo, T. Jr., Hur, J.H., Bahadorani, S., Arabyan, T., Rabie, J., Soh, J., Walker, D.W., Extension of Drosophila life span by RNAi of the mitochondrial respiratory chain. Curr. Biol. 19 (2009), 1591–1598.
93. [93] Pagliarini, D.J., Dixon, J.E., Mitochondrial modulation: reversible phosphorylation takes center stage?. Trends Biochem. Sci. 31 (2006), 26–34.
94. [94] Sohal, R.S., Orr, W.C., The redox stress hypothesis of aging. Free Radic. Biol. Med. 52 (2012), 539–555.
95. [95] Vina, J., Borras, C., Abdelaziz, K.M., Garcia-Valles, R., Gomez-Cabrera, M.C., The free radical theory of aging revisited: the cell signaling disruption theory of aging. Antioxid. Redox Signal. 19 (2013), 779–787.
96. [96] Rebrin, I., Sohal, R.S., Comparison between the effects of aging and hyperoxia on glutathione redox state and protein mixed disulfides in Drosophila melanogaster. Mech. Ageing Dev. 127 (2006), 869–874.
97. [97] Sohal, R.S., Arnold, L., Orr, W.C., Effect of age on superoxide dismutase, catalase, glutathione reductase, inorganic peroxides, TBA-reactive material, GSH/GSSG, NADPH/NADP + and NADH/NAD + in Drosophila melanogaster. Mech. Ageing Dev. 56 (1990), 223–235.
98. [98] Orr, W.C., Radyuk, S.N., Prabhudesai, L., Toroser, D., Benes, J.J., Luchak, J.M., Mockett, R.J., Rebrin, I., Hubbard, J.G., Sohal, R.S., Overexpression of glutamate–cysteine ligase extends life span in Drosophila melanogaster. J. Biol. Chem. 280 (2005), 37331–37338.
99. [99] Legan, S.K., Rebrin, I., Mockett, R.J., Radyuk, S.N., Klichko, V.I., Sohal, R.S., Orr, W.C., Overexpression of glucose-6-phosphate dehydrogenase extends the life span of Drosophila melanogaster. J. Biol. Chem. 283 (2008), 32492–32499.
100. [100] Braidy, N., Guillemin, G.J., Mansour, H., Chan-Ling, T., Poljak, A., Grant, R., Age related changes in NAD + metabolism oxidative stress and Sirt1 activity in wistar rats. PLoS One, 6, 2011, e19194.
101. [101] Gomes, A.P., Price, N.L., Ling, A.J., Moslehi, J.J., Montgomery, M.K., Rajman, L., White, J.P., Teodoro, J.S., Wrann, C.D., Hubbard, B.P., Mercken, E.M., Palmeira, C.M., de Cabo, R., Rolo, A.P., Turner, N., Bell, E.L., Sinclair, D.A., Declining NAD(+) induces a pseudohypoxic state disrupting nuclear–mitochondrial communication during aging. Cell 155 (2013), 1624–1638.
102. [102] Brand, M.D., The sites and topology of mitochondrial superoxide production. Exp. Gerontol. 45 (2010), 466–472.
103. [103] McDonagh, B., Sakellariou, G.K., Smith, N.T., Brownridge, P., Jackson, M.J., Differential cysteine labeling and global label-free proteomics reveals an altered metabolic state in skeletal muscle aging. J. Proteome Res. 13 (2014), 5008–5021.
104. [104] Menger, K.E., James, A.M., Cocheme, H.M., Harbour, M.E., Chouchani, E.T., Ding, S., Fearnley, I.M., Partridge, L., Murphy, M.P., Fasting, but not aging, dramatically alters the redox status of cysteine residues on proteins in Drosophila melanogaster. Cell Rep. 11 (2015), 1856–1865.
105. [105] Acin-Perez, R., Fernandez-Silva, P., Peleato, M.L., Perez-Martos, A., Enriquez, J.A., Respiratory active mitochondrial supercomplexes. Mol. Cell 32 (2008), 529–539.
106. [106] Lapuente-Brun, E., Moreno-Loshuertos, R., Acin-Perez, R., Latorre-Pellicer, A., Colas, C., Balsa, E., Perales-Clemente, E., Quiros, P.M., Calvo, E., Rodriguez-Hernandez, M.A., Navas, P., Cruz, R., Carracedo, A., Lopez-Otin, C., Perez-Martos, A., Fernandez-Silva, P., Fernandez-Vizarra, E., Enriquez, J.A., Supercomplex assembly determines electron flux in the mitochondrial electron transport chain. Science 340 (2013), 1567–1570.
107. [107] Maranzana, E., Barbero, G., Falasca, A.I., Lenaz, G., Genova, M.L., Mitochondrial respiratory supercomplex association limits production of reactive oxygen species from complex I. Antioxid. Redox Signal. 19 (2013), 1469–1480.
108. [108] Acin-Perez, R., Carrascoso, I., Baixauli, F., Roche-Molina, M., Latorre-Pellicer, A., Fernandez-Silva, P., Mittelbrunn, M., Sanchez-Madrid, F., Perez-Martos, A., Lowell, C.A., Manfredi, G., Enriquez, J.A., ROS-triggered phosphorylation of complex II by Fgr kinase regulates cellular adaptation to fuel use. Cell Metab. 19 (2014), 1020–1033.
109. [109] Gomez, L.A., Monette, J.S., Chavez, J.D., Maier, C.S., Hagen, T.M., Supercomplexes of the mitochondrial electron transport chain decline in the aging rat heart. Arch. Biochem. Biophys. 490 (2009), 30–35.
110. [110] Frenzel, M., Rommelspacher, H., Sugawa, M.D., Dencher, N.A., Ageing alters the supramolecular architecture of OxPhos complexes in rat brain cortex. Exp. Gerontol. 45 (2010), 563–572.
111. [111] McCord, J.M., Fridovich, I., Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J. Biol. Chem. 244 (1969), 6049–6055.
112. [112] Valko, M., Leibfritz, D., Moncol, J., Cronin, M.T., Mazur, M., Telser, J., Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol. 39 (2007), 44–84.
113. [113] Giacco, F., Brownlee, M., Oxidative stress and diabetic complications. Circ. Res. 107 (2010), 1058–1070.
114. [114] Reuter, S., Gupta, S.C., Chaturvedi, M.M., Aggarwal, B.B., Oxidative stress, inflammation, and cancer: how are they linked?. Free Radic. Biol. Med. 49 (2010), 1603–1616.
115. [115] Querfurth, H.W., LaFerla, F.M., Alzheimer's disease. N. Engl. J. Med. 362 (2010), 329–344.
116. [116] Bachschmid, M.M., Schildknecht, S., Matsui, R., Zee, R., Haeussler, D., Cohen, R.A., Pimental, D., Loo, B., Vascular aging: chronic oxidative stress and impairment of redox signaling-consequences for vascular homeostasis and disease. Ann. Med. 45 (2013), 17–36.
117. [117] Callaway, D.A., Jiang, J.X., Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone diseases. J. Bone Miner. Metab. 33 (2015), 359–370.
118. [118] Doria, E., Buonocore, D., Focarelli, A., Marzatico, F., Relationship between human aging muscle and oxidative system pathway. Oxidative Med. Cell. Longev., 2012, 2012, 830257.
119. [119] Dias, V., Junn, E., Mouradian, M.M., The role of oxidative stress in Parkinson's disease. J. Parkinsons Dis. 3 (2013), 461–491.
120. [120] Badia, M.C., Giraldo, E., Dasi, F., Alonso, D., Lainez, J.M., Lloret, A., Vina, J., Reductive stress in young healthy individuals at risk of Alzheimer disease. Free Radic. Biol. Med. 63 (2013), 274–279.
121. [121] Sanz, A., Soikkeli, M., Portero-Otin, M., Wilson, A., Kemppainen, E., McIlroy, G., Ellila, S., Kemppainen, K.K., Tuomela, T., Lakanmaa, M., Kiviranta, E., Stefanatos, R., Dufour, E., Hutz, B., Naudi, A., Jove, M., Zeb, A., Vartiainen, S., Matsuno-Yagi, A., Yagi, T., Rustin, P., Pamplona, R., Jacobs, H.T., Expression of the yeast NADH dehydrogenase Ndi1 in Drosophila confers increased lifespan independently of dietary restriction. Proc. Natl. Acad. Sci. U. S. A. 107 (2010), 9105–9110.
122. [122] Li, Z., Li, T., Yang, D., Smith, W.W., Curcumin protects against rotenone-induced neurotoxicity in cell and Drosophila models of Parkinson's disease. Adv. Parkinson's Dis. 2 (2013), 18–27.
123. [123] Keaney, M., Matthijssens, F., Sharpe, M., Vanfleteren, J., Gems, D., Superoxide dismutase mimetics elevate superoxide dismutase activity in vivo but do not retard aging in the nematode Caenorhabditis elegans. Free Radic. Biol. Med. 37 (2004), 239–250.
124. [124] Duttaroy, A., Paul, A., Kundu, M., Belton, A., A Sod2 null mutation confers severely reduced adult life span in Drosophila. Genetics 165 (2003), 2295–2299.
125. [125] Hashizume, O., Shimizu, A., Yokota, M., Sugiyama, A., Nakada, K., Miyoshi, H., Itami, M., Ohira, M., Nagase, H., Takenaga, K., Hayashi, J., Specific mitochondrial DNA mutation in mice regulates diabetes and lymphoma development. Proc. Natl. Acad. Sci. U. S. A. 109 (2012), 10528–10533.
126. [126] Schmeisser, S., Priebe, S., Groth, M., Monajembashi, S., Hemmerich, P., Guthke, R., Platzer, M., Ristow, M., Neuronal ROS signaling rather than AMPK/sirtuin-mediated energy sensing links dietary restriction to lifespan extension. Mol. Metab. 2 (2013), 92–102.
127. [127] Lawal, H.O., Chang, H.Y., Terrell, A.N., Brooks, E.S., Pulido, D., Simon, A.F., Krantz, D.E., The Drosophila vesicular monoamine transporter reduces pesticide-induced loss of dopaminergic neurons. Neurobiol. Dis. 40 (2010), 102–112.
128. [128] Fleming, S.M., Zhu, C., Fernagut, P.O., Mehta, A., DiCarlo, C.D., Seaman, R.L., Chesselet, M.F., Behavioral and immunohistochemical effects of chronic intravenous and subcutaneous infusions of varying doses of rotenone. Exp. Neurol. 187 (2004), 418–429.
129. [129] Slack, C., Foley, A., Partridge, L., Activation of AMPK by the putative dietary restriction mimetic metformin is insufficient to extend lifespan in Drosophila. PLoS One, 7, 2012, e47699.
130. [130] Liao, J., Morin, L.W., Ahmad, S.T., Methods to characterize spontaneous and startle-induced locomotion in a rotenone-induced Parkinson's disease model of Drosophila. J. Vis. Exp., 2014.
131. [131] Dillin, A., Hsu, A.L., Arantes-Oliveira, N., Lehrer-Graiwer, J., Hsin, H., Fraser, A.G., Kamath, R.S., Ahringer, J., Kenyon, C., Rates of behavior and aging specified by mitochondrial function during development. Science 298 (2002), 2398–2401.
132. [132] Liu, W., Gnanasambandam, R., Benjamin, J., Kaur, G., Getman, P.B., Siegel, A.J., Shortridge, R.D., Singh, S., Mutations in cytochrome c oxidase subunit VIa cause neurodegeneration and motor dysfunction in Drosophila. Genetics 176 (2007), 937–946.
133. [133] Burman, J.L., Itsara, L.S., Kayser, E.B., Suthammarak, W., Wang, A.M., Kaeberlein, M., Sedensky, M.M., Morgan, P.G., Pallanck, L.J., A Drosophila model of mitochondrial disease caused by a complex I mutation that uncouples proton pumping from electron transfer. Dis. Model. Mech. 7 (2014), 1165–1174.
134. [134] Celotto, A.M., Frank, A.C., McGrath, S.W., Fergestad, T., Van Voorhies, W.A., Buttle, K.F., Mannella, C.A., Palladino, M.J., Mitochondrial encephalomyopathy in Drosophila. J. Neurosci. 26 (2006), 810–820.
135. [135] Rera, M., Monnier, V., Tricoire, H., Mitochondrial electron transport chain dysfunction during development does not extend lifespan in Drosophila melanogaster. Mech. Ageing Dev. 131 (2010), 156–164.
136. [136] Houtkooper, R.H., Mouchiroud, L., Ryu, D., Moullan, N., Katsyuba, E., Knott, G., Williams, R.W., Auwerx, J., Mitonuclear protein imbalance as a conserved longevity mechanism. Nature 497 (2013), 451–457.
137. [137] Mouchiroud, L., Houtkooper, R.H., Moullan, N., Katsyuba, E., Ryu, D., Canto, C., Mottis, A., Jo, Y.S., Viswanathan, M., Schoonjans, K., Guarente, L., Auwerx, J., The NAD(+)/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell 154 (2013), 430–441.
138. [138] Bennett, C.F., Vander Wende, H., Simko, M., Klum, S., Barfield, S., Choi, H., Pineda, V.V., Kaeberlein, M., Activation of the mitochondrial unfolded protein response does not predict longevity in Caenorhabditis elegans. Nat. Commun., 5, 2014, 3483.
139. [139] Dell'agnello, C., Leo, S., Agostino, A., Szabadkai, G., Tiveron, C., Zulian, A., Prelle, A., Roubertoux, P., Rizzuto, R., Zeviani, M., Increased longevity and refractoriness to Ca(2 +)-dependent neurodegeneration in Surf1 knockout mice. Hum. Mol. Genet. 16 (2007), 431–444.
140. [140] Liu, X., Jiang, N., Hughes, B., Bigras, E., Shoubridge, E., Hekimi, S., Evolutionary conservation of the clk-1-dependent mechanism of longevity: loss of mclk1 increases cellular fitness and lifespan in mice. Genes Dev. 19 (2005), 2424–2434.
141. [141] Civiletto, G., Varanita, T., Cerutti, R., Gorletta, T., Barbaro, S., Marchet, S., Lamperti, C., Viscomi, C., Scorrano, L., Zeviani, M., Opa1 overexpression ameliorates the phenotype of two mitochondrial disease mouse models. Cell Metab. 21 (2015), 845–854.
142. [142] Metodiev, M.D., Lesko, N., Park, C.B., Camara, Y., Shi, Y., Wibom, R., Hultenby, K., Gustafsson, C.M., Larsson, N.G., Methylation of 12S rRNA is necessary for in vivo stability of the small subunit of the mammalian mitochondrial ribosome. Cell Metab. 9 (2009), 386–397.
143. [143] Lapointe, J., Hekimi, S., Early mitochondrial dysfunction in long-lived Mclk1 +/− mice. J. Biol. Chem. 283 (2008), 26217–26227.
144. [144] Pulliam, D.A., Deepa, S.S., Liu, Y., Hill, S., Lin, A.L., Bhattacharya, A., Shi, Y., Sloane, L., Viscomi, C., Zeviani, M., Van Remmen, H., Complex IV-deficient Surf1(−/−) mice initiate mitochondrial stress responses. Biochem. J. 462 (2014), 359–371.
145. [145] Parkes, T.L., Elia, A.J., Dickinson, D., Hilliker, A.J., Phillips, J.P., Boulianne, G.L., Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons. Nat. Genet. 19 (1998), 171–174.
146. [146] Sun, J., Folk, D., Bradley, T.J., Tower, J., Induced overexpression of mitochondrial Mn-superoxide dismutase extends the life span of adult Drosophila melanogaster. Genetics 161 (2002), 661–672.
147. [147] Stefanatos, R., Sriram, A., Kiviranta, E., Mohan, A., Ayala, V., Jacobs, H.T., Pamplona, R., Sanz, A., dj-1beta regulates oxidative stress, insulin-like signaling and development in Drosophila melanogaster. Cell Cycle 11 (2012), 3876–3886.
148. [148] Sohal, R.S., Effect of hydrogen peroxide administration on life span, superoxide dismutase, catalase, and glutathione in the adult housefly, Musca domestica. Exp. Gerontol. 23 (1988), 211–216.
149. [149] Mockett, R.J., Sohal, B.H., Sohal, R.S., Expression of multiple copies of mitochondrially targeted catalase or genomic Mn superoxide dismutase transgenes does not extend the life span of Drosophila melanogaster. Free Radic. Biol. Med. 49 (2010), 2028–2031.
150. [150] Orr, W.C., Mockett, R.J., Benes, J.J., Sohal, R.S., Effects of overexpression of copper–zinc and manganese superoxide dismutases, catalase, and thioredoxin reductase genes on longevity in Drosophila melanogaster. J. Biol. Chem. 278 (2003), 26418–26422.
151. [151] Lavara-Culebras, E., Munoz-Soriano, V., Gomez-Pastor, R., Matallana, E., Paricio, N., Effects of pharmacological agents on the lifespan phenotype of Drosophila DJ-1beta mutants. Gene 462 (2010), 26–33.
152. [152] Cabreiro, F., Ackerman, D., Doonan, R., Araiz, C., Back, P., Papp, D., Braeckman, B.P., Gems, D., Increased life span from overexpression of superoxide dismutase in Caenorhabditis elegans is not caused by decreased oxidative damage. Free Radic. Biol. Med. 51 (2011), 1575–1582.
153. [153] Doonan, R., McElwee, J.J., Matthijssens, F., Walker, G.A., Houthoofd, K., Back, P., Matscheski, A., Vanfleteren, J.R., Gems, D., Against the oxidative damage theory of aging: superoxide dismutases protect against oxidative stress but have little or no effect on life span in Caenorhabditis elegans. Genes Dev. 22 (2008), 3236–3241.
154. [154] Gardner, R., Salvador, A., Moradas-Ferreira, P., Why does SOD overexpression sometimes enhance, sometimes decrease, hydrogen peroxide production? A minimalist explanation. Free Radic. Biol. Med. 32 (2002), 1351–1357.
155. [155] Schriner, S.E., Linford, N.J., Martin, G.M., Treuting, P., Ogburn, C.E., Emond, M., Coskun, P.E., Ladiges, W., Wolf, N., Van Remmen, H., Wallace, D.C., Rabinovitch, P.S., Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308 (2005), 1909–1911.
156. [156] Choi, C.Q., Old Mice Hard to Replicate. The Scientist, 2007.
157. [157] Olahova, M., Taylor, S.R., Khazaipoul, S., Wang, J., Morgan, B.A., Matsumoto, K., Blackwell, T.K., Veal, E.A., A redox-sensitive peroxiredoxin that is important for longevity has tissue- and stress-specific roles in stress resistance. Proc. Natl. Acad. Sci. U. S. A. 105 (2008), 19839–19844.
158. [158] Lee, K.S., Iijima-Ando, K., Iijima, K., Lee, W.J., Lee, J.H., Yu, K., Lee, D.S., JNK/FOXO-mediated neuronal expression of fly homologue of peroxiredoxin II reduces oxidative stress and extends life span. J. Biol. Chem. 284 (2009), 29454–29461.
159. [159] Neumann, C.A., Krause, D.S., Carman, C.V., Das, S., Dubey, D.P., Abraham, J.L., Bronson, R.T., Fujiwara, Y., Orkin, S.H., Van Etten, R.A., Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression. Nature 424 (2003), 561–565.
160. [160] Radyuk, S.N., Michalak, K., Klichko, V.I., Benes, J., Rebrin, I., Sohal, R.S., Orr, W.C., Peroxiredoxin 5 confers protection against oxidative stress and apoptosis and also promotes longevity in Drosophila. Biochem. J. 419 (2009), 437–445.
161. [161] Mitozo, P.A., de Souza, L.F., Loch-Neckel, G., Flesch, S., Maris, A.F., Figueiredo, C.P., Dos Santos, A.R., Farina, M., Dafre, A.L., A study of the relative importance of the peroxiredoxin-, catalase-, and glutathione-dependent systems in neural peroxide metabolism. Free Radic. Biol. Med. 51 (2011), 69–77.
162. [162] Zhu, C.T., Ingelmo, P., Rand, D.M., GxGxE for lifespan in Drosophila: mitochondrial, nuclear, and dietary interactions that modify longevity. PLoS Genet., 10, 2014, e1004354.
163. [163] Rera, M., Bahadorani, S., Cho, J., Koehler, C.L., Ulgherait, M., Hur, J.H., Ansari, W.S., Lo, T. Jr., Jones, D.L., Walker, D.W., Modulation of longevity and tissue homeostasis by the drosophila PGC-1 homolog. Cell Metab. 14 (2011), 623–634.