Established Principles and Emerging Concepts on the Interplay between Mitochondrial Physiology and S-(De)nitrosylation: Implications in Cancer and Neurodegeneration
S-nitrosylation is a posttranslational modification of cysteine residues that has been frequently indicated as potential molecular mechanism governing cell response upon redox unbalance downstream of nitric oxide (over)production. In the last years, increased levels of S-nitrosothiols (SNOs) have been tightly associated with the onset of nitroxidative stress-based pathologies (e.g., cancer and neurodegeneration), conditions in which alterations of mitochondrial homeostasis and activation of cellular processes dependent on it have been reported as well. In this paper we aim at summarizing the current knowledge of mitochondria-related proteins undergoing S-nitrosylation and how this redox modification might impact on mitochondrial functions, whose impairment has been correlated to tumorigenesis and neuronal cell death. In particular, emphasis will be given to the possible, but still neglected implication of denitrosylation reactions in the modulation of mitochondrial SNOs and how they can affect mitochondrion-related cellular process, such as oxidative phosphorylation, mitochondrial dynamics, and mitophagy. 1. Introduction Nitric oxide (NO) is a gaseous and membrane diffusible radical molecule generated by the NADPH-dependent enzyme NO synthase (NOS) from L-arginine and oxygen [1, 2]. Three are the major isoforms of NOS that have been so far identified, namely, neuronal and endothelial NOS (nNOS or NOS1 and eNOS or NOS3, resp.), which are constitutively active, and the cytokine-inducible NOS (iNOS or NOS2), mainly expressed in immune system to face host attack [3, 4]. The biochemical characterization of NO as new signaling molecule, as well as its implication in cardiovascular function earned Furchgott, Ignarro, and Murad the Nobel prize in Physiology or Medicine in 1998. In particular, they provided the most consistent lines of evidence that NO activates guanylyl cyclase by a direct binding to heme iron (Fe-nitrosylation) and induces cGMP-mediated signaling [5], thus regulating blood vessel tone [6], immune response [7], neurotransmission [8], and many other organic functions. NO can also react with other oxygen-derived radical and nonradical species (ROS), thus generating more dangerous reactive nitrogen species (RNS, e.g., peroxynitrite, ONOO？), which target proteins and irreversibly affect their structure and function, a phenomenon commonly known as nitrosative (or nitroxidative) stress [9]. Tyrosine nitration is one of the modifications occurring under conditions of NO overproduction and mostly depends on the reaction with ONOO？ [10]. It consists of
References
[1]
M. A. Marletta, “Nitric oxide synthase: aspects concerning structure and catalysis,” Cell, vol. 78, no. 6, pp. 927–930, 1994.
[2]
O. W. Griffith and D. J. Stuehr, “Nitric oxide synthases: properties and catalytic mechanism,” Annual Review of Physiology, vol. 57, pp. 707–736, 1995.
[3]
T. Michel and O. Feron, “Nitric oxide synthases: which, where, how, and why?” The Journal of Clinical Investigation, vol. 100, no. 9, pp. 2146–2152, 1997.
[4]
R. G. Knowles and S. Moncada, “Nitric oxide synthases in mammals,” Biochemical Journal, vol. 298, no. 2, pp. 249–258, 1994.
[5]
R. M. Rapoport, M. B. Draznin, and F. Murad, “Endothelium-dependent relaxation in rat aorta may be mediated through cyclic GMP-dependent protein phosphorylation,” Nature, vol. 306, no. 5939, pp. 174–176, 1983.
[6]
R. M. J. Palmer, A. G. Ferrige, and S. Moncada, “Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor,” Nature, vol. 327, no. 6122, pp. 524–526, 1987.
[7]
C. Bogdan, “Nitric oxide and the immune response,” Nature Immunology, vol. 2, no. 10, pp. 907–916, 2001.
[8]
J. R. Steinert, S. W. Robinson, H. Tong, M. D. Haustein, C. Kopp-Scheinpflug, and I. D. Forsythe, “Nitric oxide is an activity-dependent regulator of target neuron intrinsic excitability,” Neuron, vol. 71, no. 2, pp. 291–305, 2011.
[9]
J. S. Beckman and W. H. Koppenol, “Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and the ugly,” American Journal of Physiology, vol. 271, no. 5, pp. C1424–C1437, 1996.
[10]
J. S. Beckman, “Oxidative damage and tyrosine nitration from peroxynitrite,” Chemical Research in Toxicology, vol. 9, no. 5, pp. 836–844, 1996.
[11]
H. Ischiropoulos, “Protein tyrosine nitration-An update,” Archives of Biochemistry and Biophysics, vol. 484, no. 2, pp. 117–121, 2009.
[12]
J. R. Lee, J. K. Kim, S. J. Lee, and K. P. Kim, “Role of protein tyrosine nitration in neurodegenerative diseases and atherosclerosis,” Archives of Pharmacal Research, vol. 32, no. 8, pp. 1109–1118, 2009.
[13]
T. Uehara, “Accumulation of misfolded protein through nitrosative stress linked to neurodegenerative disorders,” Antioxidants and Redox Signaling, vol. 9, no. 5, pp. 597–601, 2007.
[14]
J. M. Souza, G. Peluffo, and R. Radi, “Protein tyrosine nitration-Functional alteration or just a biomarker?” Free Radical Biology and Medicine, vol. 45, no. 4, pp. 357–366, 2008.
[15]
D. T. Hess, A. Matsumoto, S. O. Kim, H. E. Marshall, and J. S. Stamler, “Protein S-nitrosylation: purview and parameters,” Nature Reviews Molecular Cell Biology, vol. 6, no. 2, pp. 150–166, 2005.
[16]
M. W. Foster, D. T. Hess, and J. S. Stamler, “Protein S-nitrosylation in health and disease: a current perspective,” Trends in Molecular Medicine, vol. 15, no. 9, pp. 391–404, 2009.
[17]
J. S. Stamler, S. Lamas, and F. C. Fang, “Nitrosylation: the prototypic redox-based signaling mechanism,” Cell, vol. 106, no. 6, pp. 675–683, 2001.
[18]
Z. Gu, M. Kaul, B. Yan et al., “S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death,” Science, vol. 297, no. 5584, pp. 1186–1190, 2002.
[19]
M. Benhar, M. T. Forrester, and J. S. Stamler, “Protein denitrosylation: enzymatic mechanisms and cellular functions,” Nature Reviews Molecular Cell Biology, vol. 10, no. 10, pp. 721–732, 2009.
[20]
M. Benhar, M. T. Forrester, D. T. Hess, and J. S. Stamler, “Regulated protein denitrosylation by cytosolic and mitochondrial thioredoxins,” Science, vol. 320, no. 5879, pp. 1050–1054, 2008.
[21]
A. Holmgren, “Biochemistry: SNO removal,” Science, vol. 320, no. 5879, pp. 1019–1020, 2008.
[22]
F. Beigi, D. R. Gonzalez, K. M. Minhas et al., “Dynamic denitrosylation via S-nitrosoglutathione reductase regulates cardiovascular function,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 11, pp. 4314–4319, 2012.
[23]
D. E. Jensen, G. K. Belka, and G. C. Du Bois, “S-nitrosoglutathione is a substrate for rat alcohol dehydrogenase class III isoenzyme,” Biochemical Journal, vol. 331, no. 2, pp. 659–668, 1998.
[24]
S. J. Chinta and J. K. Andersen, “Nitrosylation and nitration of mitochondrial complex i in Parkinson's disease,” Free Radical Research, vol. 45, no. 1, pp. 53–58, 2011.
[25]
C. A. Piantadosi, “Regulation of mitochondrial processes by protein S-nitrosylation,” Biochimica et Biophysica Acta, vol. 1820, no. 6, pp. 712–721, 2011.
[26]
S. Moncada and J. D. Erusalimsky, “Does nitric oxide modulate mitochondrial energy generation and apoptosis?” Nature Reviews Molecular Cell Biology, vol. 3, no. 3, pp. 214–220, 2002.
[27]
L. Castro, V. Demicheli, V. Tórtora, and R. Radi, “Mitochondrial protein tyrosine nitration,” Free Radical Research, vol. 45, no. 1, pp. 37–52, 2011.
[28]
J. P. Collman, A. Dey, R. A. Decreau et al., “Interaction of nitric oxide with a functional model of cytochrome c oxidase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 29, pp. 9892–9896, 2008.
[29]
G. C. Brown, “Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidase,” FEBS Letters, vol. 356, no. 2-3, pp. 295–298, 1994.
[30]
G. C. Brown, “Nitric oxide regulates mitochondrial respiration and cell functions by inhibiting cytochrome oxidase,” FEBS Letters, vol. 369, no. 2-3, pp. 136–139, 1995.
[31]
M. Schweizer and C. Richter, “Nitric oxide potently and reversibly deenergizes mitochondria at low oxygen tension,” Biochemical and Biophysical Research Communications, vol. 204, no. 1, pp. 169–175, 1994.
[32]
G. C. Brown, “Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome c oxidase,” Biochimica et Biophysica Acta, vol. 1504, no. 1, pp. 46–57, 2001.
[33]
M. G. Mason, P. Nicholls, M. T. Wilson, and C. E. Cooper, “Nitric oxide inhibition of respiration involves both competitive (heme) and noncompetitive (copper) binding to cytochrome c oxidase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 3, pp. 708–713, 2006.
[34]
L. S. Burwell, S. M. Nadtochiy, A. J. Tompkins, S. Young, and P. S. Brookes, “Direct evidence for S-nitrosation of mitochondrial complex I,” Biochemical Journal, vol. 394, no. 3, pp. 627–634, 2006.
[35]
E. Clementi, G. C. Brown, M. Feelisch, and S. Moncada, “Persistent inhibition of cell respiration by nitric oxide: crucial role of S-nitrosylation of mitochondrial complex I and protective action of glutathione,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 13, pp. 7631–7636, 1998.
[36]
J. Sun, M. Morgan, R. F. Shen, C. Steenbergen, and E. Murphy, “Preconditioning results in S-nitrosylation of proteins involved in regulation of mitochondrial energetics and calcium transport,” Circulation Research, vol. 101, no. 11, pp. 1155–1163, 2007.
[37]
J. Zhang, B. Jin, L. Li, E. R. Block, and J. M. Patel, “Nitric oxide-induced persistent inhibition and nitrosylation of active site cysteine residues of mitochondrial cytochrome-c oxidase in lung endothelial cells,” American Journal of Physiology, vol. 288, no. 4, pp. C840–C849, 2005.
[38]
H. Noji and M. Yoshida, “The rotary machine in the cell, ATP synthase,” The Journal of Biological Chemistry, vol. 276, no. 3, pp. 1665–1668, 2001.
[39]
B. Westermann, “Mitochondrial fusion and fission in cell life and death,” Nature Reviews Molecular Cell Biology, vol. 11, no. 12, pp. 872–884, 2010.
[40]
L. C. Gomes, G. D. Benedetto, and L. Scorrano, “During autophagy mitochondria elongate, are spared from degradation and sustain cell viability,” Nature Cell Biology, vol. 13, no. 5, pp. 589–598, 2011.
[41]
D. C. Chan, “Mitochondria: dynamic organelles in disease, aging, and development,” Cell, vol. 125, no. 7, pp. 1241–1252, 2006.
[42]
D. C. Chan, “Mitochondrial fusion and fission in mammals,” Annual Review of Cell and Developmental Biology, vol. 22, pp. 79–99, 2006.
[43]
A. Devin and M. Rigoulet, “Mechanisms of mitochondrial response to variations in energy demand in eukaryotic cells,” American Journal of Physiology, vol. 292, no. 1, pp. C52–C58, 2007.
[44]
G. Twig and O. S. Shirihai, “The interplay between mitochondrial dynamics and mitophagy,” Antioxidants and Redox Signaling, vol. 14, no. 10, pp. 1939–1951, 2011.
[45]
C. Rouzier, S. Bannwarth, A. Chaussenot et al., “The MFN2 gene is responsible for mitochondrial DNA instability and optic atrophy “plus” phenotype,” Brain, vol. 135, no. 1, pp. 23–34, 2012.
[46]
S. Cipolat, O. M. De Brito, B. Dal Zilio, and L. Scorrano, “OPA1 requires mitofusin 1 to promote mitochondrial fusion,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 45, pp. 15927–15932, 2004.
[47]
C. R. Chang and C. Blackstone, “Dynamic regulation of mitochondrial fission through modification of the dynamin-related protein Drp1,” Annals of the New York Academy of Sciences, vol. 1201, pp. 34–39, 2010.
[48]
H. Chen, A. Chomyn, and D. C. Chan, “Disruption of fusion results in mitochondrial heterogeneity and dysfunction,” The Journal of Biological Chemistry, vol. 280, no. 28, pp. 26185–26192, 2005.
[49]
H. Chen, S. A. Detmer, A. J. Ewald, E. E. Griffin, S. E. Fraser, and D. C. Chan, “Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development,” Journal of Cell Biology, vol. 160, no. 2, pp. 189–200, 2003.
[50]
A. Olichon, L. J. Emorine, E. Descoins et al., “The human dynamin-related protein OPA1 is anchored to the mitochondrial inner membrane facing the inter-membrane space,” FEBS Letters, vol. 523, no. 1–3, pp. 171–176, 2002.
[51]
R. Yamaguchi, L. Lartigue, G. Perkins et al., “Opa1-mediated cristae opening is Bax/Bak and BH3 dependent, required for apoptosis, and independent of Bak oligomerization,” Molecular Cell, vol. 31, no. 4, pp. 557–569, 2008.
[52]
P. Huang, C. A. Galloway, and Y. Yoon, “Control of mitochondrial morphology through differential interactions of mitochondrial fusion and fission proteins,” PLoS ONE, vol. 6, no. 5, Article ID e20655, 2011.
[53]
S. Lee, S. Y. Jeong, W. C. Lim et al., “Mitochondrial fission and fusion mediators, hFis1 and OPA1, modulate cellular senescence,” The Journal of Biological Chemistry, vol. 282, no. 31, pp. 22977–22983, 2007.
[54]
K. Yamano and R. J. Youle, “Coupling mitochondrial and cell division,” Nature Cell Biology, vol. 13, no. 9, pp. 1026–1027, 2011.
[55]
X. J. Han, Y. F. Lu, S. A. Li et al., “CaM kinase Iα-induced phosphorylation of Drp1 regulates mitochondrial morphology,” Journal of Cell Biology, vol. 182, no. 3, pp. 573–585, 2008.
[56]
N. Taguchi, N. Ishihara, A. Jofuku, T. Oka, and K. Mihara, “Mitotic phosphorylation of dynamin-related GTPase Drp1 participates in mitochondrial fission,” The Journal of Biological Chemistry, vol. 282, no. 15, pp. 11521–11529, 2007.
[57]
A. S. Dickey and S. Strack, “PKA/AKAP1 AND PP2A/Bβ2 regulate neuronal morphogenesis via Drp1 phosphorylation and mitochondrial bioenergetics,” Journal of Neuroscience, vol. 31, no. 44, pp. 15716–15726, 2011.
[58]
G. M. Cereghetti, A. Stangherlin, O. Martins De Brito et al., “Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 41, pp. 15803–15808, 2008.
[59]
D. H. Cho, T. Nakamura, J. Fang et al., “β-Amyloid-related mitochondrial fission and neuronal injury,” Science, vol. 324, no. 5923, pp. 102–105, 2009.
[60]
B. Bossy, A. Petrilli, E. Klinglmayr et al., “S-nitrosylation of DRP1 does not affect enzymatic activity and is not specific to Alzheimer's disease,” Journal of Alzheimer's Disease, vol. 20, no. 2, pp. S513–S526, 2010.
[61]
F. Cecconi and B. Levine, “The role of autophagy in mammalian development: cell makeover rather than cell death,” Developmental Cell, vol. 15, no. 3, pp. 344–357, 2008.
[62]
G. Kroemer, G. Mari？o, and B. Levine, “Autophagy and the integrated cell response,” Molecular Cell, vol. 40, no. 2, pp. 280–293, 2010.
[63]
D. Narendra, A. Tanaka, D. F. Suen, and R. J. Youle, “Parkin is recruited selectively to impaired mitochondria and promotes their autophagy,” Journal of Cell Biology, vol. 183, no. 5, pp. 795–803, 2008.
[64]
L. C. Gomes and L. Scorrano, “Mitochondrial morphology in mitophagy and macroautophagy,” Biochimica et Biophysica Acta. In press.
[65]
V. G. Grivennikova, A. V. Kareyeva, and A. D. Vinogradov, “What are the sources of hydrogen peroxide production by heart mitochondria?” Biochimica et Biophysica Acta, vol. 1797, no. 6-7, pp. 939–944, 2010.
[66]
J. Lee, S. Giordano, and J. Zhang, “Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling,” Biochemical Journal, vol. 441, no. 2, pp. 523–540, 2012.
[67]
H. Takano-Ohmuro, M. Mukaida, E. Kominami, and K. Morioka, “Autophagy in embryonic erythroid cells: its role in maturation,” European Journal of Cell Biology, vol. 79, no. 10, pp. 759–764, 2000.
[68]
S. P. Elmore, T. Qian, S. F. Grissom, and J. J. Lemasters, “The mitochondrial permeability transition initiates autophagy in rat hepatocytes,” The FASEB Journal, vol. 15, no. 12, pp. 2286–2287, 2001.
[69]
G. Twig, A. Elorza, A. J. A. Molina et al., “Fission and selective fusion govern mitochondrial segregation and elimination by autophagy,” The EMBO Journal, vol. 27, no. 2, pp. 433–446, 2008.
[70]
S. M. Jin, M. Lazarou, C. Wang, L. A. Kane, D. P. Narendra, and R. J. Youle, “Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL,” Journal of Cell Biology, vol. 191, no. 5, pp. 933–942, 2010.
[71]
G. Shi, J. R. Lee, D. A. Grimes et al., “Functional alteration of PARL contributes to mitochondrial dysregulation in Parkinson's disease,” Human Molecular Genetics, vol. 20, no. 10, Article ID ddr077, pp. 1966–1974, 2011.
[72]
S. Geisler, K. M. Holmstr？m, D. Skujat et al., “PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1,” Nature Cell Biology, vol. 12, no. 2, pp. 119–131, 2010.
[73]
A. Tanaka, M. M. Cleland, S. Xu et al., “Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin,” Journal of Cell Biology, vol. 191, no. 7, pp. 1367–1380, 2010.
[74]
L. J. Pallanck, “Culling sick mitochondria from the herd,” Journal of Cell Biology, vol. 191, no. 7, pp. 1225–1227, 2010.
[75]
D. Yao, Z. Gu, T. Nakamura et al., “Nitrosative stress linked to sporadic Parkinson's disease: S-nitrosylation of parkin regulates its E3 ubiquitin ligase activity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 29, pp. 10810–10814, 2004.
[76]
F. Meng, D. Yao, Y. Shi et al., “Oxidation of the cysteine-rich regions of parkin perturbs its E3 ligase activity and contributes to protein aggregation,” Molecular Neurodegeneration, vol. 6, no. 1, article 34, 2011.
[77]
J. Y. Lee, Y. Nagano, J. P. Taylor, K. L. Lim, and T. P. Yao, “Disease-causing mutations in Parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy,” Journal of Cell Biology, vol. 189, no. 4, pp. 671–679, 2010.
[78]
C. Hubbert, A. Guardiola, R. Shao et al., “HDAC6 is a microtubule-associated deacetylase,” Nature, vol. 417, no. 6887, pp. 455–458, 2002.
[79]
Y. Zilberman, C. Ballestrem, L. Carramusa, R. Mazitschek, S. Khochbin, and A. Bershadsky, “Regulation of microtubule dynamics by inhibition of the tubulin deacetylase HDAC6,” Journal of Cell Science, vol. 122, no. 19, pp. 3531–3541, 2009.
[80]
N. A. Reed, D. Cai, T. L. Blasius et al., “Microtubule acetylation promotes kinesin-1 binding and transport,” Current Biology, vol. 16, no. 21, pp. 2166–2172, 2006.
[81]
A. Nott, P. M. Watson, J. D. Robinson, L. Crepaldi, and A. Riccio, “S-nitrosylation of histone deacetylase 2 induces chromatin remodelling in neurons,” Nature, vol. 455, no. 7211, pp. 411–415, 2008.
[82]
D. Watson and A. Riccio, “Nitric oxide and histone deacetylases a new relationship between old molecules,” Communitative and Integrative Biology, vol. 2, no. 1, pp. 11–13, 2009.
[83]
P. J. Kahle, J. Waak, and T. Gasser, “DJ-1 and prevention of oxidative stress in Parkinson's disease and other age-related disorders,” Free Radical Biology and Medicine, vol. 47, no. 10, pp. 1354–1361, 2009.
[84]
X. Wang, T. G. Petrie, Y. Liu, J. Liu, H. Fujioka, and X. Zhu, “Parkinson's disease-associated DJ-1 mutations impair mitochondrial dynamics and cause mitochondrial dysfunction,” Journal of Neurochemistry, vol. 121, no. 5, pp. 830–839, 2012.
[85]
G. Krebiehl, S. Ruckerbauer, L. F. Burbulla et al., “Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinson's disease-associated protein DJ-1,” PLoS ONE, vol. 5, no. 2, Article ID e9367, 2010.
[86]
M. A. Wilson, “The role of cysteine oxidation in DJ-1 function and dysfunction,” Antioxidants and Redox Signaling, vol. 15, no. 1, pp. 111–122, 2011.
[87]
H. Ren, K. Fu, D. Wang, C. Mu, and G. Wang, “Oxidized DJ-1 interacts with the mitochondrial protein BCL-X L,” The Journal of Biological Chemistry, vol. 286, no. 40, pp. 35308–35317, 2011.
[88]
G. Ito, H. Ariga, Y. Nakagawa, and T. Iwatsubo, “Roles of distinct cysteine residues in S-nitrosylation and dimerization of DJ-1,” Biochemical and Biophysical Research Communications, vol. 339, no. 2, pp. 667–672, 2006.
[89]
B. Fadeel and S. Orrenius, “Apoptosis: a basic biological phenomenon with wide-ranging implications in human disease,” Journal of Internal Medicine, vol. 258, no. 6, pp. 479–517, 2005.
[90]
M. E. Soriano and L. Scorrano, “The interplay between BCL-2 family proteins and mitochondrial morphology in the regulation of apoptosis,” Advances in Experimental Medicine and Biology, vol. 687, pp. 97–114, 2010.
[91]
D. D. Thomas, L. A. Ridnour, J. S. Isenberg et al., “The chemical biology of nitric oxide: implications in cellular signaling,” Free Radical Biology and Medicine, vol. 45, no. 1, pp. 18–31, 2008.
[92]
C. M. Schonhoff, B. Gaston, and J. B. Mannick, “Nitrosylation of cytochrome c during apoptosis,” The Journal of Biological Chemistry, vol. 278, no. 20, pp. 18265–18270, 2003.
[93]
N. Azad, V. Vallyathan, L. Wang et al., “S-nitrosylation of Bcl-2 inhibits its ubiquitin-proteasomal degradation: a novel antiapoptotic mechanism that suppresses apoptosis,” The Journal of Biological Chemistry, vol. 281, no. 45, pp. 34124–34134, 2006.
[94]
D. E. Burger, X. Lu, M. Lei et al., “Neuronal nitric oxide synthase protects against myocardial infarction-induced ventricular arrhythmia and mortality in mice,” Circulation, vol. 120, no. 14, pp. 1345–1354, 2009.
[95]
T. T. Nguyen, M. V. Stevens, M. Kohr, C. Steenbergen, M. N. Sack, and E. Murphy, “Cysteine 203 of cyclophilin D is critical for cyclophilin D activation of the mitochondrial permeability transition pore,” The Journal of Biological Chemistry, vol. 286, no. 46, pp. 40184–40192, 2011.
[96]
H. Ohtani, H. Katoh, T. Tanaka et al., “Effects of nitric oxide on mitochondrial permeability transition pore and thiol-mediated responses in cardiac myocytes,” Nitric Oxide, vol. 26, no. 2, pp. 95–101, 2012.
[97]
S. Hortelano, B. Dallaporta, N. Zamzami et al., “Nitric oxide induces apoptosis via triggering mitochondrial permeability transition,” FEBS Letters, vol. 410, no. 2-3, pp. 373–377, 1997.
[98]
J. B. Mannick, C. Schonhoff, N. Papeta et al., “S-nitrosylation of mitochondrial caspases,” Journal of Cell Biology, vol. 154, no. 6, pp. 1111–1116, 2001.
[99]
G. Melino, F. Bernassola, R. A. Knight, M. T. Corasaniti, G. Nisticò, and A. Finazzi-Agrò, “S-nitrosylation regulates apoptosis,” Nature, vol. 388, no. 6641, pp. 432–433, 1997.
[100]
S. Dimmeler, J. Haendeler, M. Nehls, and A. M. Zeiher, “Suppression of apoptosis by nitric oxide via inhibition of interleukin- 1β-converting enzyme (ICE)-like and cysteine protease protein (CPP)-32-like proteases,” Journal of Experimental Medicine, vol. 185, no. 4, pp. 601–607, 1997.
[101]
J. Li, T. R. Billiar, R. V. Talanian, and Y. M. Kim, “Nitric oxide reversibly inhibits seven members of the caspase family via S-nitrosylation,” Biochemical and Biophysical Research Communications, vol. 240, no. 2, pp. 419–424, 1997.
[102]
J. B. Mannick, A. Hausladen, L. Liu et al., “Fas-induced caspase denitrosylation,” Science, vol. 284, no. 5414, pp. 651–654, 1999.
[103]
L. Leon-Bollotte, S. Subramaniam, O. Cauvard et al., “S-Nitrosylation of the death receptor Fas promotes Fas ligandmediated apoptosis in cancer cells,” Gastroenterology, vol. 140, no. 7, pp. 2009–2018, 2011.
[104]
V. Haynes, S. Elfering, N. Traaseth, and C. Giulivi, “Mitochondrial nitric-oxide synthase: enzyme expression, characterization, and regulation,” Journal of Bioenergetics and Biomembranes, vol. 36, no. 4, pp. 341–346, 2004.
[105]
Z. Lacza, E. Pankotai, A. Csordás et al., “Mitochondrial NO and reactive nitrogen species production: does mtNOS exist?” Nitric Oxide, vol. 14, no. 2, pp. 162–168, 2006.
[106]
P. R. Castello, P. S. David, T. McClure, Z. Crook, and R. O. Poyton, “Mitochondrial cytochrome oxidase produces nitric oxide under hypoxic conditions: implications for oxygen sensing and hypoxic signaling in eukaryotes,” Cell Metabolism, vol. 3, no. 4, pp. 277–287, 2006.
[107]
D. E. Handy and J. Loscalzo, “Redox regulation of mitochondrial function,” Antioxidants and Redox Signaling, vol. 16, no. 11, pp. 1323–1367, 2012.
[108]
A. Ferri, P. Fiorenzo, M. Nencini et al., “Glutaredoxin 2 prevents aggregation of mutant SOD1 in mitochondria and abolishes its toxicity,” Human Molecular Genetics, vol. 19, no. 22, pp. 4529–4542, 2010.
[109]
C. H. Lillig, C. Berndt, and A. Holmgren, “Glutaredoxin systems,” Biochimica et Biophysica Acta, vol. 1780, no. 11, pp. 1304–1317, 2008.
[110]
S. I. Hashemy, C. Johansson, C. Berndt, C. H. Lillig, and A. Holmgren, “Oxidation and S-nitrosylation of cysteines in human cytosolic and mitochondrial glutaredoxins: effects on structure and activity,” The Journal of Biological Chemistry, vol. 282, no. 19, pp. 14428–14436, 2007.
[111]
J. M. Romero and O. A. Bizzozero, “Intracellular glutathione mediates the denitrosylation of protein nitrosothiols in the rat spinal cord,” Journal of Neuroscience Research, vol. 87, no. 3, pp. 701–709, 2009.
[112]
L. G. Que, Z. Yang, J. S. Stamler, N. L. Lugogo, and M. Kraft, “S-nitrosoglutathione reductase: an important regulator in human asthma,” American Journal of Respiratory and Critical Care Medicine, vol. 180, no. 3, pp. 226–231, 2009.
[113]
L. G. Que, L. Liu, Y. Yan et al., “Biomedicine: protection from experimental asthma by an endogenous bronchodilator,” Science, vol. 308, no. 5728, pp. 1618–1621, 2005.
[114]
L. Liu, Y. Yan, M. Zeng et al., “Essential roles of S-nitrosothiols in vascular homeostasis and endotoxic shock,” Cell, vol. 116, no. 4, pp. 617–628, 2004.
[115]
B. Lima, G. K. W. Lam, L. Xie et al., “Endogenous S-nitrosothiols protect against myocardial injury,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 15, pp. 6297–6302, 2009.
[116]
Z. Yang, Z. E. Wang, P. T. Doulias et al., “Lymphocyte development requires S-nitrosoglutathione reductase,” The Journal of Immunology, vol. 185, no. 11, pp. 6664–6669, 2010.
[117]
W. Wei, B. Li, M. A. Hanes, S. Kakar, X. Chen, and L. Liu, “S-nitrosylation from GSNOR deficiency impairs DNA repair and promotes hepatocarcinogenesis,” Science Translational Medicine, vol. 2, no. 19, p. 19ra13, 2010.
[118]
W. Wei, Z. Yang, C. H. Tang, and L. Liu, “Targeted deletion of GSNOR in hepatocytes of mice causes nitrosative inactivation of O6-alkylguanine-dna alkyltransferase and increased sensitivity to genotoxic diethylnitrosamine,” Carcinogenesis, vol. 32, no. 7, pp. 973–977, 2011.
[119]
D. Galter, A. Carmine, S. Buervenich, G. Duester, and L. Olson, “Distribution of class I, III and IV alcohol dehydrogenase mRNAS in the adult rat, mouse and human brain,” European Journal of Biochemistry, vol. 270, no. 6, pp. 1316–1326, 2003.
[120]
H. Wiseman and B. Halliwell, “Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer,” Biochemical Journal, vol. 313, no. 1, pp. 17–29, 1996.
[121]
Z. Gu, T. Nakamura, and S. A. Lipton, “Redox reactions induced by nitrosative stress mediate protein misfolding and mitochondrial dysfunction in neurodegenerative diseases,” Molecular Neurobiology, vol. 41, no. 2-3, pp. 55–72, 2010.
[122]
T. Nakamura and S. A. Lipton, “Cell death: protein misfolding and neurodegenerative diseases,” Apoptosis, vol. 14, no. 4, pp. 455–468, 2009.
[123]
D. Ziech, R. Franco, A. Pappa, and M. I. Panayiotidis, “Reactive Oxygen Species (ROS)—induced genetic and epigenetic alterations in human carcinogenesis,” Mutation Research, vol. 711, no. 1-2, pp. 167–173, 2011.
[124]
W. H. Koppenol, P. L. Bounds, and C. V. Dang, “Otto Warburg's contributions to current concepts of cancer metabolism,” Nature Reviews Cancer, vol. 11, no. 5, pp. 325–337, 2011.
[125]
R. A. Cairns, I. S. Harris, and T. W. Mak, “Regulation of cancer cell metabolism,” Nature Reviews Cancer, vol. 11, no. 2, pp. 85–95, 2011.
[126]
J. Aragonés, P. Fraisl, M. Baes, and P. Carmeliet, “Oxygen sensors at the crossroad of metabolism,” Cell Metabolism, vol. 9, no. 1, pp. 11–22, 2009.
[127]
A. J. Majmundar, W. J. Wong, and M. C. Simon, “Hypoxia-inducible factors and the response to hypoxic stress,” Molecular Cell, vol. 40, no. 2, pp. 294–309, 2010.
[128]
E. L. Page, D. A. Chan, A. J. Giaccia, M. Levine, and D. E. Richard, “Hypoxia-inducible factor-1α stabilization in nonhypoxic conditions: role of oxidation and intracellular ascorbate depletion,” Molecular Biology of the Cell, vol. 19, no. 1, pp. 86–94, 2008.
[129]
E. Metzen, J. Zhou, W. Jelkmann, J. Fandrey, and B. Brüne, “Nitric oxide impairs normoxic degradation of HIF-1α by inhibition of prolyl hydroxylases,” Molecular Biology of the Cell, vol. 14, no. 8, pp. 3470–3481, 2003.
[130]
Y. Sha and H. E. Marshall, “S-nitrosylation in the regulation of gene transcription,” Biochimica et Biophysica Acta, vol. 1820, no. 6, pp. 701–711, 2011.
[131]
F. Li, P. Sonveaux, Z. N. Rabbani et al., “Regulation of HIF-1α Stability through S-Nitrosylation,” Molecular Cell, vol. 26, no. 1, pp. 63–74, 2007.
[132]
K. Kirito, Y. Hu, and N. Komatsu, “HIF-1 prevents the overproduction of mitochondrial ROS after cytokine stimulation through induction of PDK-1,” Cell Cycle, vol. 8, no. 17, pp. 2844–2849, 2009.
[133]
G. L. Semenza, “Mitochondrial autophagy: life and breath of the cell,” Autophagy, vol. 4, no. 4, pp. 534–536, 2008.
[134]
A. Herrero-Mendez, A. Almeida, E. Fernández, C. Maestre, S. Moncada, and J. P. Bola？os, “The bioenergetic and antioxidant status of neurons is controlled by continuous degradation of a key glycolytic enzyme by APC/C-Cdh1,” Nature Cell Biology, vol. 11, no. 6, pp. 747–752, 2009.
[135]
J. P. Bola？os, A. Almeida, and S. Moncada, “Glycolysis: a bioenergetic or a survival pathway?” Trends in Biochemical Sciences, vol. 35, no. 3, pp. 145–149, 2010.
[136]
S. Fernandez-Fernandez, A. Almeida, and J. P. Bola？os, “Antioxidant and bioenergetic coupling between neurons and astrocytes,” Biochemical Journal, vol. 443, no. 1, pp. 3–11, 2012.
[137]
T. Nguyen, P. Nioi, and C. B. Pickett, “The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress,” The Journal of Biological Chemistry, vol. 284, no. 20, pp. 13291–13295, 2009.
[138]
J. D. Hayes, A. T. Dinkova-Kostova, and M. Mcmahon, “Cross-talk between transcription factors AhR and Nrf2: lessons for cancer chemoprevention from dioxin,” Toxicological Sciences, vol. 111, no. 2, pp. 199–201, 2009.
[139]
G. M. Denicola, F. A. Karreth, T. J. Humpton et al., “Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis,” Nature, vol. 475, no. 7354, pp. 106–110, 2011.
[140]
S. Fourquet, R. Guerois, D. Biard, and M. B. Toledano, “Activation of NRF2 by nitrosative agents and H2O2 involves KEAP1 disulfide formation,” The Journal of Biological Chemistry, vol. 285, no. 11, pp. 8463–8471, 2010.
[141]
C. Q. Li, Y. K. Min, L. C. Godoy, A. Thiantanawat, L. J. Trudel, and G. N. Wogan, “Nitric oxide activation of Keap1/Nrf2 signaling in human colon carcinoma cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 34, pp. 14547–14551, 2009.
[142]
H. C. Um, J. H. Jang, D. H. Kim, C. Lee, and Y. J. Surh, “Nitric oxide activates Nrf2 through S-nitrosylation of Keap1 in PC12 cells,” Nitric Oxide, vol. 25, no. 2, pp. 161–168, 2011.
[143]
H. Broholm, I. Rubin, A. Kruse et al., “Nitric oxide synthase expression and enzymatic activity in human brain tumors,” Clinical Neuropathology, vol. 22, no. 6, pp. 273–281, 2003.
[144]
Y. Z. Wang, Y. Q. Cao, J. N. Wu, M. Chen, and X. Y. Cha, “Expression of nitric oxide synthase in human gastric carcinoma and its relation to p53, PCNA,” World Journal of Gastroenterology, vol. 11, no. 1, pp. 46–50, 2005.
[145]
S. Ambs, W. P. Bennett, W. G. Merriam et al., “Vascular endothelial growth factor and nitric oxide synthase expression in human lung cancer and the relation to p53,” British Journal of Cancer, vol. 78, no. 2, pp. 233–239, 1998.
[146]
S. Ambs, W. G. Merriam, M. O. Ogunfusika et al., “p53 and vascular endothelial growth factor regulate tumor growth of NOS2-expressing human carcinoma cells,” Nature Medicine, vol. 4, no. 12, pp. 1371–1376, 1998.
[147]
D. F. Calvisi, F. Pinna, S. Ladu et al., “Aberrant iNOS signaling is under genetic control in rodent liver cancer and potentially prognostic for the human disease,” Carcinogenesis, vol. 29, no. 8, pp. 1639–1647, 2008.
[148]
E. Atik, Y. Onlen, L. Savas, and F. Doran, “Inducible nitric oxide synthase and histopathological correlation in chronic viral hepatitis,” International Journal of Infectious Diseases, vol. 12, no. 1, pp. 12–15, 2008.
[149]
L. McNaughton, L. Puttagunta, M. A. Martinez-Cuesta et al., “Distribution of nitric oxide synthase in normal and cirrhotic human liver,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 26, pp. 17161–17166, 2002.
[150]
C. H. Tang, W. Wei, and L. Liu, “Regulation of DNA repair by S-nitrosylation,” Biochimica et Biophysica Acta, vol. 1820, no. 6, pp. 730–735, 2011.
[151]
E. I. Rugarli and T. Langer, “Mitochondrial quality control: a matter of life and death for neurons,” The EMBO Journal, vol. 31, no. 6, pp. 1336–1349, 2012.
[152]
H. Harris and D. C. Rubinsztein, “Control of autophagy as a therapy for neurodegenerative disease,” Nature Reviews Neurology, vol. 8, no. 2, pp. 108–117, 2012.
[153]
C. Perier and M. Vila, “Mitochondrial biology and Parkinson's disease,” Cold Spring Harbor Perspective in Medicine, vol. 2, no. 2, Article ID a009332, 2012.
[154]
B. I. Giasson, J. E. Duda, I. V. J. Murray et al., “Oxidative damage linked to neurodegeneration by selective α-synuclein nitration in synucleinopathy lesions,” Science, vol. 290, no. 5493, pp. 985–989, 2000.
[155]
D. Liu, F. Bao, J. Wen, and J. Liu, “Mutation of superoxide dismutase elevates reactive species: comparison of nitration and oxidation of proteins in different brain regions of transgenic mice with amyotrophic lateral sclerosis,” Neuroscience, vol. 146, no. 1, pp. 255–264, 2007.
[156]
E. C. Stack, W. R. Matson, and R. J. Ferrante, “Evidence of oxidant damage in Huntington's disease: translational strategies using antioxidants,” Annals of the New York Academy of Sciences, vol. 1147, pp. 79–92, 2008.
[157]
T. Nakamura and S. A. Lipton, “Emerging roles of S-nitrosylation in protein misfolding and neurodegenerative diseases,” Antioxidants and Redox Signaling, vol. 10, no. 1, pp. 87–101, 2008.
[158]
J. Fang, T. Nakamura, D. H. Cho, Z. Gu, and S. A. Lipton, “S-nitrosylation of peroxiredoxin 2 promotes oxidative stress-induced neuronal cell death in Parkinson's disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 47, pp. 18742–18747, 2007.
[159]
A. H. K. Tsang, Y. I. L. Lee, H. S. Ko et al., “S-nitrosylation of XIAP compromises neuronal survival in Parkinson's disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 12, pp. 4900–4905, 2009.
[160]
K. J. Conn, W. Gao, A. McKee et al., “Identification of the protein disulfide isomerase family member PDIp in experimental Parkinson's disease and Lewy body pathology,” Brain Research, vol. 1022, no. 1-2, pp. 164–172, 2004.
[161]
T. Uehara, T. Nakamura, D. Yao et al., “S-Nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration,” Nature, vol. 441, no. 7092, pp. 513–517, 2006.
[162]
A. Ventruti and A. M. Cuervo, “Autophagy and neurodegeneration,” Current Neurology and Neuroscience Reports, vol. 7, no. 5, pp. 443–451, 2007.
[163]
B. I. Giasson and V. M. Y. Lee, “Are ubiquitination pathways central to Parkinson's disease?” Cell, vol. 114, no. 1, pp. 1–8, 2003.
[164]
F. Janku, D. J. McConkey, D. S. Hong, and R. Kurzrock, “Autophagy as a target for anticancer therapy,” Nature Reviews Clinical Oncology, vol. 8, pp. 528–539, 2011.
[165]
V. Kirkin and I. Dikic, “Ubiquitin networks in cancer,” Current Opinion in Genetics and Development, vol. 21, no. 1, pp. 21–28, 2011.
[166]
J. Tyedmers, A. Mogk, and B. Bukau, “Cellular strategies for controlling protein aggregation,” Nature Reviews Molecular Cell Biology, vol. 11, no. 11, pp. 777–788, 2010.
[167]
E. Wong and A. M. Cuervo, “Integration of clearance mechanisms: the proteasome and autophagy,” Cold Spring Harbor Perspectives in Biology, vol. 2, no. 12, Article ID a006734, 2010.
[168]
B. Ravikumar and D. C. Rubinsztein, “Can autophagy protect against neurodegeneration caused by aggregate-prone proteins?” NeuroReport, vol. 15, no. 16, pp. 2443–2445, 2004.
[169]
D. C. Rubinsztein, M. DiFiglia, N. Heintz et al., “Autophagy and its possible roles in nervous system diseases, damage and repair,” Autophagy, vol. 1, no. 1, pp. 11–22, 2005.
[170]
S. Sarkar, V. I. Korolchuk, M. Renna et al., “Complex inhibitory effects of nitric oxide on autophagy,” Molecular Cell, vol. 43, no. 1, pp. 19–32, 2011.
[171]
H. Wei and J.-L. Guan, “Pro-tumorigenic function of autophagy in mammary oncogenesis,” Autophagy, vol. 8, no. 1, pp. 129–131, 2012.
[172]
A. C. Kimmelman, “The dynamic nature of autophagy in cancer,” Genes and Development, vol. 25, no. 19, pp. 1999–2010, 2011.
[173]
F. Lozy and V. Karantza, “Autophagy and cancer cell metabolism,” Seminars in Cell and Developmental Biology, vol. 23, no. 4, pp. 395–401, 2012.
[174]
M. Dewaele, H. Maes, and P. Agostinis, “ROS-mediated mechanisms of autophagy stimulation and their relevance in cancer therapy,” Autophagy, vol. 6, no. 7, pp. 838–854, 2010.
[175]
M. B. Azad, Y. Chen, and S. B. Gibson, “Regulation of autophagy by reactive oxygen species (ROS): implications for cancer progression and treatment,” Antioxidants and Redox Signaling, vol. 11, no. 4, pp. 777–790, 2009.
[176]
N. Mizushima, “Autophagy in protein and organelle turnover,” Cold Spring Harbor Symposia on Quantitative Biology, vol. 76, pp. 397–402, 2011.
[177]
E. Morselli, L. Galluzzi, O. Kepp et al., “Oncosuppressive functions of autophagy,” Antioxidants and Redox Signaling, vol. 14, no. 11, pp. 2251–2269, 2011.
[178]
U. E. Martinez-Outschoorn, D. Whitaker-Menezes, S. Pavlides et al., “The autophagic tumor stroma model of cancer or “battery-operated tumor growth”: a simple solution to the autophagy paradox,” Cell Cycle, vol. 9, no. 21, pp. 4297–4306, 2010.
[179]
Y.-L. Hu, M. DeLay, A. Jahangiri et al., “Hypoxia-induced autophagy promotes tumor cell survival and adaptation to antiangiogenic treatment in glioblastoma,” Cancer Research, vol. 72, no. 7, pp. 1773–1783, 2012.
[180]
R. Mathew, C. M. Karp, B. Beaudoin et al., “Autophagy suppresses tumorigenesis through elimination of p62,” Cell, vol. 137, no. 6, pp. 1062–1075, 2009.
[181]
M. Komatsu, H. Kurokawa, S. Waguri et al., “The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1,” Nature Cell Biology, vol. 12, no. 3, pp. 213–223, 2010.
[182]
R. J. Youle and D. P. Narendra, “Mechanisms of mitophagy,” Nature Reviews Molecular Cell Biology, vol. 12, no. 1, pp. 9–14, 2011.
[183]
S. Geisler, K. M. Holmstr？m, A. Treis et al., “The PINK1/Parkin-mediated mitophagy is compromised by PD-associated mutations,” Autophagy, vol. 6, no. 7, pp. 871–878, 2010.
[184]
E. Deas, N. W. Wood, and H. Plun-Favreau, “Mitophagy and Parkinson's disease: the PINK1-parkin link,” Biochimica et Biophysica Acta, vol. 1813, no. 4, pp. 623–633, 2011.
[185]
D. P. Narendra, L. A. Kane, D. N. Hauser, I. M. Fearnley, and R. J. Youle, “p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both,” Autophagy, vol. 6, no. 8, pp. 1090–1106, 2010.
[186]
A. Grünewald, L. Voges, A. Rakovic et al., “Mutant parkin impairs mitochondrial function and morphology in human fibroblasts,” PLoS ONE, vol. 5, no. 9, Article ID e12962, 2010.
[187]
K. K. K. Chung, B. Thomas, X. Li et al., “S-nitrosylation of parkin regulates ubiquitination and compromises parkin's protective function,” Science, vol. 304, no. 5675, pp. 1328–1331, 2004.
[188]
L. Glauser, S. Sonnay, K. Stafa, and D. J. Moore, “Parkin promotes the ubiquitination and degradation of the mitochondrial fusion factor mitofusin 1,” Journal of Neurochemistry, vol. 118, no. 4, pp. 636–645, 2011.
[189]
S. J. Baloyannis, “Mitochondrial alterations in Alzheimer's disease,” Journal of Alzheimer's Disease, vol. 9, no. 2, pp. 119–126, 2006.
[190]
M. J. Barsoum, H. Yuan, A. A. Gerencser et al., “Nitric oxide-induced mitochondrial fission is regulated by dynamin-related GTPases in neurons,” The EMBO Journal, vol. 25, no. 16, pp. 3900–3911, 2006.
[191]
X. Wang, B. Su, H. G. Lee et al., “Impaired balance of mitochondrial fission and fusion in Alzheimer's disease,” Journal of Neuroscience, vol. 29, no. 28, pp. 9090–9103, 2009.
[192]
M. Manczak, M. J. Calkins, and P. H. Reddy, “Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer's disease: implications for neuronal damage,” Human Molecular Genetics, vol. 20, no. 13, pp. 2495–2509, 2011.
[193]
H. Yuan, A. A. Gerencser, G. Liot et al., “Mitochondrial fission is an upstream and required event for bax foci formation in response to nitric oxide in cortical neurons,” Cell Death and Differentiation, vol. 14, no. 3, pp. 462–471, 2007.
[194]
B. Westermann, “Nitric oxide links mitochondrial fission to alzheimer's disease,” Science Signaling, vol. 2, no. 69, p. pe29, 2009.
[195]
P. C. Zeidler, J. R. Roberts, V. Castranova et al., “Response of alveolar macrophages from inducible nitric oxide synthase knockout or wild-type mice to an in vitro lipopolysaccharide or silica exposure,” Journal of Toxicology and Environmental Health—Part A, vol. 66, no. 11, pp. 995–1013, 2003.
[196]
J. I. Chao, P. C. Kuo, and T. S. Hsu, “Down-regulation of survivin in nitric oxide induced cell growth inhibition and apoptosis of the human lung carcinoma cells,” The Journal of Biological Chemistry, vol. 279, no. 19, pp. 20267–20276, 2004.
[197]
M. R. Ciriolo, A. De Martino, E. Lafavia, L. Rossi, M. T. Carrì, and G. Rotilio, “Cu,Zn-superoxide dismutase-dependent apoptosis induced by nitric oxide in neuronal cells,” The Journal of Biological Chemistry, vol. 275, no. 7, pp. 5065–5072, 2000.
[198]
B. Brüne, J. Zhou, and A. Von Knethen, “Nitric oxide, oxidative stress, and apoptosis,” Kidney International, Supplement, vol. 63, no. 84, pp. S22–S24, 2003.
[199]
O. Gallo, E. Masini, L. Morbidelli et al., “Role of nitric oxide in angiogenesis and tumor progression in head and neck cancer,” Journal of the National Cancer Institute, vol. 90, no. 8, pp. 587–596, 1998.
[200]
B. Fitzpatrick, M. Mehibel, R. L. Cowen, and I. J. Stratford, “iNOS as a therapeutic target for treatment of human tumors,” Nitric Oxide, vol. 19, no. 2, pp. 217–224, 2008.
[201]
G. M. Tiboni and E. Clementini, “Teratological consequences of nitric oxide synthesis inhibition,” Current Pharmaceutical Design, vol. 10, no. 22, pp. 2759–2767, 2004.
[202]
A. B. Knott and E. Bossy-Wetzel, “Impact of nitric oxide on metabolism in health and age-related disease,” Diabetes, Obesity and Metabolism, vol. 12, no. 2, pp. S126–S133, 2010.
[203]
W. S. Liang, E. M. Reiman, J. Valla et al., “Alzheimer's disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 11, pp. 4441–4446, 2008.
[204]
W. D. Parker, J. Parks, C. M. Filley, and B. K. Kleinschmidt-DeMasters, “Electron transport chain defects in Alzheimer's disease brain,” Neurology, vol. 44, no. 6, pp. 1090–1096, 1994.
[205]
P. H. Reddy, “Mitochondrial dysfunction in aging and Alzheimer's disease: strategies to protect neurons,” Antioxidants and Redox Signaling, vol. 9, no. 10, pp. 1647–1658, 2007.
[206]
G. Bernard, N. Bellance, D. James et al., “Mitochondrial bioenergetics and structural network organization,” Journal of Cell Science, vol. 120, no. 5, pp. 838–848, 2007.
[207]
T. Yu, J. L. Robotham, and Y. Yoon, “Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 8, pp. 2653–2658, 2006.
[208]
L. Peng, X. Men, W. Zhang et al., “Dynamin-related protein 1 is implicated in endoplasmic reticulum stress-induced pancreatic β-cell apoptosis,” International Journal of Molecular Medicine, vol. 28, no. 2, pp. 161–169, 2011.
[209]
P. C. Sanghani, W. I. Davis, S. L. Fears et al., “Kinetic and cellular characterization of novel inhibitors of S-nitrosoglutathione reductase,” The Journal of Biological Chemistry, vol. 284, no. 36, pp. 24354–24362, 2009.
[210]
M. Hellgren, J. Carlsson, L. J. ？stberg, C. A. Staab, B. Persson, and J. O. H？？g, “Enrichment of ligands with molecular dockings and subsequent characterization for human alcohol dehydrogenase 3,” Cellular and Molecular Life Sciences, vol. 67, no. 17, pp. 3005–3015, 2010.
[211]
X. Sun, J. Qiu, S. A. Strong et al., “Structure-activity relationships of pyrrole based S-nitrosoglutathione reductase inhibitors: pyrrole regioisomers and propionic acid replacement,” Bioorganic and Medicinal Chemistry Letters, vol. 21, no. 12, pp. 3671–3675, 2011.
