Strategic localization of heart mitochondrial NOS: A review of the evidence

American Journal of Physiology - Heart and Circulatory Physiology

Volumn 303, Issue 11, 2012, Pages

  Zaobornyj, Tamara ^a   Ghafourifar, Pedram ^b  

^a UNIVERSIDAD DE BUENOS AIRES   (Argentina)

^b Tri State Institute of Pharmaceutical Sciences   (United States)

Author keywords

Calcium; Hypoxia; Ischemia reperfusion; Mitochondrial nitric oxide synthase; Transmembrane potential

Indexed keywords

ARGININE; CALCIUM; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; OXYGEN;

BIOCHEMISTRY; CELLULAR DISTRIBUTION; ENZYME ACTIVITY; ENZYME LOCALIZATION; HEART MITOCHONDRION; HEART MUSCLE; HEART MUSCLE CELL; HEART MUSCLE METABOLISM; HUMAN; MITOCHONDRIAL MEMBRANE POTENTIAL; NONHUMAN; PRIORITY JOURNAL; REVIEW;

ANIMALS; HEART; HUMANS; MEMBRANE POTENTIALS; MITOCHONDRIA, HEART; MODELS, ANIMAL; MYOCARDIUM; NITRIC OXIDE; NITRIC OXIDE SYNTHASE;

EID: 84870545221     PISSN: 03636135     EISSN: 15221539     Source Type: Journal    
DOI: 10.1152/ajpheart.00674.2011     Document Type: Review

References (146)

1. Abadir PM, Foster DB, Crow M, Cooke CA, Rucker JJ, Jain A, Smith BJ, Burks TN, Cohn RD, Fedarko NS, Carey RM, O'Rourke B, Walston JD. Identification and characterization of a functional mitochondrial angiotensin system. Proc Natl Acad Sci USA 108: 14849-14854, 2011.
2. Acuna-Castroviejo D, Escames G, Leon J, Carazo A, Khaldy H. Mitochondrial regulation by melatonin and its metabolites. Adv Exp Med Biol 527: 549-557, 2003.
3. Alvarez S, Boveris A. Mitochondrial nitric oxide metabolism in rat muscle during endotoxemia. Free Radic Biol Med 37: 1472-1478, 2004.
4. Antunes F, Boveris A, Cadenas E. On the mechanism and biology of cytochrome oxidase inhibition by nitric oxide. Proc Natl Acad Sci USA 101: 16774-16779, 2004.
5. Antunes F, Boveris A, Cadenas E. On the biologic role of the reaction of NO with oxidized cytochrome c oxidase. Antioxid Redox Signal 9: 1569-1579, 2007.
6. Baker JE, Holman P, Kalyanaraman B, Griffith OW, Pritchard KA Jr. Adaptation to chronic hypoxia confers tolerance to subsequent myocardial ischemia by increased nitric oxide production. Ann NY Acad Sci 874: 236-253, 1999.
7. Balligand JL, Kobzik L, Han X, Kaye DM, Belhassen L, O'Hara DS, Kelly RA, Smith TW, Michel T. Nitric oxide-dependent parasympathetic signaling is due to activation of constitutive endothelial (type III) nitric oxide synthase in cardiac myocytes. J Biol Chem 270: 14582-14586, 1995.
8. Balligand JL, Ungureanu-Longrois D, Simmons WW, Pimental D, Malinski TA, Kapturczak M, Taha Z, Lowenstein CJ, Davidoff AJ, Kelly RA, Smith TW, and Michel T. Cytokine-inducible nitric oxide synthase (iNOS) expression in cardiac myocytes. Characterization and regulation of iNOS expression and detection of iNOS activity in single cardiac myocytes in vitro. J Biol Chem 269: 27580-27588, 1994.
9. Barouch LA, Harrison RW, Skaf MW, Rosas GO, Cappola TP, Kobeissi ZA, Hobai IA, Lemmon CA, Burnett AL, O'Rourke B, Rodriguez ER, Huang PL, Lima JA, Berkowitz DE, Hare JM. Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms. Nature 416: 337-339, 2002.
10. Bates TE, Loesch A, Burnstock G, Clark JB. Mitochondrial nitric oxide synthase: a ubiquitous regulator of oxidative phosphorylation? Biochem Biophys Res Commun 218: 40-44, 1996.
11. Bell EL, Emerling BM, Chandel NS. Mitochondrial regulation of oxygen sensing. Mitochondrion 5: 322-332, 2005.
12. Bopassa JC, Michel P, Gateau-Roesch O, Ovize M, Ferrera R. Low-pressure reperfusion alters mitochondrial permeability transition. Am J Physiol Heart Circ Physiol 288: H2750-H2755, 2005.
13. Borutaite V, Brown GC. Rapid reduction of nitric oxide by mitochondria, and reversible inhibition of mitochondrial respiration by nitric oxide. Biochem J 315: 295-299, 1996.
14. Borutaite V, Budriunaite A, Brown GC. Reversal of nitric oxide-, peroxynitrite-and S-nitrosothiol-induced inhibition of mitochondrial respiration or complex I activity by light and thiols. Biochim Biophys Acta 1459: 405-412, 2000.
15. Boveris A, Oshino N, Chance B. The cellular production of hydrogen peroxide. Biochem J 128: 617-630, 1972.
16. Boveris A, D'Amico G, Lores-Arnaiz S, Costa LE. Enalapril increases mitochondrial nitric oxide synthase activity in heart and liver. Antioxid Redox Signal 5: 691-697, 2003.
17. Boveris A, Valdez LB, Zaobornyj T, Bustamante J. Mitochondrial metabolic states regulate nitric oxide and hydrogen peroxide diffusion to the cytosol. Biochim Biophys Acta 1757: 535-542, 2006.
18. Boveris DL, Boveris A. Oxygen delivery to the tissues and mitochondrial respiration. Front Biosci 12: 1014-1023, 2007.
19. 2+ release. Free Radic Biol Med 29: 343-348, 2000.
20. Brodsky SV, Gao S, Li H, Goligorsky MS. Hyperglycemic switch from mitochondrial nitric oxide to superoxide production in endothelial cells. Am J Physiol Heart Circ Physiol 283: H2130-H2139, 2002.
21. Brookes PS. Mitochondrial nitric oxide synthase. Mitochondrion 3: 187-204, 2004.
22. Brookes PS, Salinas EP, Darley-Usmar K, Eiserich JP, Freeman BA, Darley-Usmar VM, Anderson PG. Concentration-dependent effects of nitric oxide on mitochondrial permeability transition and cytochrome c release. J Biol Chem 275: 20474-20479, 2000.
23. Brookes PS, Kraus DW, Shiva S, Doeller JE, Barone MC, Patel RP, Lancaster JR Jr, Darley-Usmar V. Control of mitochondrial respiration by NO*, effects of low oxygen and respiratory state. J Biol Chem 278: 31603-31609, 2003.
24. Brown GC, Cooper CE. Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidase. FEBS Lett 356: 295-298, 1994.
25. Burwell LS, Nadtochiy SM, Tompkins AJ, Young S, Brookes PS. Direct evidence for S-nitrosation of mitochondrial complex I. Biochem J 394: 627-634, 2006.
26. Cleeter MW, Cooper JM, Darley-Usmar VM, Moncada S, Schapira AH. Reversible inhibition of cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, by nitric oxide. Implications for neurodegenerative diseases. FEBS Lett 345: 50-54, 1994.
27. Clerc P, Rigoulet M, Leverve X, Fontaine E. Nitric oxide increases oxidative phosphorylation efficiency. J Bioenerg Biomembr 39: 158-166, 2007.
28. Coburn RF, Ploegmakers F, Gondrie P, Abboud R. Myocardial myoglobin oxygen tension. Am J Physiol 224: 870-876, 1973.
29. Costa LE, Boveris A, Koch OR, Taquini AC. Liver and heart mitochondria in rats submitted to chronic hypobaric hypoxia. Am J Physiol Cell Physiol 255: C123-C129, 1988.
30. Costa LE, La-Padula P, Lores-Arnaiz S, D'Amico G, Boveris A, Kurnjek ML, Basso N. Long-term angiotensin II inhibition increases mitochondrial nitric oxide synthase and not antioxidant enzyme activities in rat heart. J Hypertens 20: 2487-2494, 2002.
31. Crompton M. The mitochondrial permeability transition pore and its role in cell death. Biochem J 341: 233-249, 1999.
32. Csordas A, Pankotai E, Snipes JA, Cselenyak A, Sarszegi Z, Cziraki A, Gaszner B, Papp L, Benko R, Kiss L, Kovacs E, Kollai M, Szabo C, Busija DW, Lacza Z. Human heart mitochondria do not produce physiologically relevant quantities of nitric oxide. Life Sci 80: 633-637, 2007.
33. Darley-Usmar V. The powerhouse takes control of the cell; the role of mitochondria in signal transduction. Free Radic Biol Med 37: 753-754, 2004.
34. Davidson SM, Duchen MR. Effects of NO on mitochondrial function in cardiomyocytes: Pathophysiological relevance. Cardiovasc Res 71: 10-21, 2006.
35. De Belder AJ, Radomski MW, Why HJ, Richardson PJ, Bucknall CA, Salas E, Martin JF, Moncada S. Nitric oxide synthase activities in human myocardium. Lancet 341: 84-85, 1993.
36. 2+ by nitric oxide in cultured bovine vascular endothelial cells. Am J Physiol Cell Physiol 289: C836-C845, 2005.
37. 2+ and the heart. Cell Calcium 44: 77-91, 2008.
38. Dedkova EN, Blatter LA. Characteristics and function of cardiac mitochondrial nitric oxide synthase. J Physiol 587: 851-872, 2009.
39. Dedkova EN, Ji X, Lipsius SL, Blatter LA. Mitochondrial calcium uptake stimulates nitric oxide production in mitochondria of bovine vascular endothelial cells. Am J Physiol Cell Physiol 286: C406-C415, 2004.
40. Desrois M, Sciaky M, Lan C, Cozzone PJ, Bernard M. Preservation of amino acids during long term ischemia and subsequent reflow with supplementation of L-arginine, the nitric oxide precursor, in the rat heart. Amino Acids 24: 141-148, 2003.
41. Duranski MR, Greer JJ, Dejam A, Jaganmohan S, Hogg N, Langston W, Patel RP, Yet SF, Wang X, Kevil CG, Gladwin MT, Lefer DJ. Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver. J Clin Invest 115: 1232-1240, 2005.
42. Elfering SL, Sarkela TM, Giulivi C. Biochemistry of mitochondrial nitric oxide synthase. J Biol Chem 277: 38079-38086, 2002.
43. Fellet AL, Balaszczuk AM, Arranz C, Lopez-Costa JJ, Boveris A, Bustamante J. Autonomic regulation of pacemaker activity: role of heart nitric oxide synthases. Am J Physiol Heart Circ Physiol 291: H1246-H1254, 2006.
44. Feron O, Belhassen L, Kobzik L, Smith TW, Kelly RA, Michel T. Endothelial nitric oxide synthase targeting to caveolae. Specific interactions with caveolin isoforms in cardiac myocytes and endothelial cells. J Biol Chem 271: 22810-22814, 1996.
45. ATPchannels. Am J Physiol Heart Circ Physiol 288: H62-H68, 2005.
46. Forkel J, Chen X, Wandinger S, Keser F, Duschin A, Schwanke U, Frede S, Massoudy P, Schulz R, Jakob H, Heusch G. Responses of chronically hypoxic rat hearts to ischemia: KATP channel blockade does not abolish increased RV tolerance to ischemia. Am J Physiol Heart Circ Physiol 286: H545-H551, 2004.
47. Franco MC, Arciuch VG, Peralta JG, Galli S, Levisman D, Lopez LM, Romorini L, Poderoso JJ, Carreras MC. Hypothyroid phenotype is contributed by mitochondrial complex I inactivation due to translocated neuronal nitric-oxide synthase. J Biol Chem 281: 4779-4786, 2006.
48. French S, Giulivi C, Balaban RS. Nitric oxide synthase in porcine heart mitochondria: evidence for low physiological activity. Am J Physiol Heart Circ Physiol 280: H2863-H2867, 2001.
49. Fridovich I. Superoxide radical and superoxide dismutases. Annu Rev Biochem 64: 97-112, 1995.
50. Gao S, Chen J, Brodsky SV, Huang H, Adler S, Lee JH, Dhadwal N, Cohen-Gould L, Gross SS, Goligorsky MS. Docking of endothelial nitric oxide synthase (eNOS) to the mitochondrial outer membrane: a pentabasic amino acid sequence in the autoinhibitory domain of eNOS targets a proteinase K-cleavable peptide on the cytoplasmic face of mitochondria. J Biol Chem 279: 15968-15974, 2004.
51. Ghafourifar P, Parihar MS, Nazarewicz R, Zenebe WJ, Parihar A. Detection assays for determination of mitochondrial nitric oxide synthase activity; advantages and limitations. Methods Enzymol 440: 317-334, 2008.
52. Ghafourifar P, Richter C. Nitric oxide synthase activity in mitochondria. FEBS Lett 418: 291-296, 1997.
53. Ghafourifar P, Richter C. Mitochondrial nitric oxide synthase regulates mitochondrial matrix pH. Biol Chem 380: 1025-1028, 1999.
54. Ghafourifar P, Schenk U, Klein SD, Richter C. Mitochondrial nitricoxide synthase stimulation causes cytochrome c release from isolated mitochondria. Evidence for intramitochondrial peroxynitrite formation. J Biol Chem 274: 31185-31188, 1999.
55. Ghafourifar P, Klein SD, Schucht O, Schenk U, Pruschy M, Rocha S, Richter C. Ceramide induces cytochrome c release from isolated mitochondria. Importance of mitochondrial redox state. J Biol Chem 274: 6080-6084, 1999.
56. Giulivi C, Poderoso JJ, Boveris A. Production of nitric oxide by mitochondria. J Biol Chem 273: 11038-11043, 1998.
57. Gnaiger E, Steinlechner-Maran R, Mendez G, Eberl T, Margreiter R. Control of mitochondrial and cellular respiration by oxygen. J Bioenerg Biomembr 27: 583-596, 1995.
58. Gonzales GF, Chung FA, Miranda S, Valdez LB, Zaobornyj T, Bustamante J, Boveris A. Heart mitochondrial nitric oxide synthase is upregulated in male rats exposed to high altitude (4,340 m). Am J Physiol Heart Circ Physiol 288: H2568-H2573, 2005.
59. Gottlieb RA, Burleson KO, Kloner RA, Babior BM, Engler RL. Reperfusion injury induces apoptosis in rabbit cardiomyocytes. J Clin Invest 94: 1621-1628, 1994.
60. Grilli A, De Lutiis MA, Patruno A, Speranza L, Cataldi A, Centurione L, Taccardi AA, Di Napoli P, De Caterina R, Barbacane R, Conti P, Felaco M. Effect of chronic hypoxia on inducible nitric oxide synthase expression in rat myocardial tissue. Exp Biol Med (Maywood) 228: 935-942, 2003.
61. Hare JM. Nitric oxide and excitation-contraction coupling. J Mol Cell Cardiol 35: 719-729, 2003.
62. Hare JM, Lofthouse RA, Juang GJ, Colman L, Ricker KM, Kim B, Senzaki H, Cao S, Tunin RS, Kass DA. Contribution of caveolin protein abundance to augmented nitric oxide signaling in conscious dogs with pacing-induced heart failure. Circ Res 86: 1085-1092, 2000.
63. Haywood GA, Tsao PS, Von Der Leyen H. E, Mann MJ, Keeling PJ, Trindade PT, Lewis NP, Byrne CD, Rickenbacher PR, Bishopric NH, Cooke JP, Mckenna WJ, Fowler MB. Expression of inducible nitric oxide synthase in human heart failure. Circulation 93: 1087-1094, 1996.
64. Hotta Y, Otsuka-Murakami H, Fujita M, Nakagawa J, Yajima M, Liu W, Ishikawa N, Kawai N, Masumizu T, Kohno M. Protective role of nitric oxide synthase against ischemia-reperfusion injury in guinea pig myocardial mitochondria. Eur J Pharmacol 380: 37-48, 1999.
65. Ignarro LJ. Heart mtNOS, a key mediator of oxidative injury in ischemia/reperfusion. J Mol Cell Cardiol 43: 409-410, 2007.
66. Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 84: 9265-9269, 1987.
67. Jung AS, Kubo H, Wilson R, Houser SR, Margulies KB. Modulation of contractility by myocyte-derived arginase in normal and hypertrophied feline myocardium. Am J Physiol Heart Circ Physiol 290: H1756-H1762, 2006.
68. Kanai A, Epperly M, Pearce L, Birder L, Zeidel M, Meyers S, Greenberger J, De Groat W, Apodaca G, Peterson J. Differing roles of mitochondrial nitric oxide synthase in cardiomyocytes and urothelial cells. Am J Physiol Heart Circ Physiol 286: H13-H21, 2004.
69. Kanai AJ, Mesaros S, Finkel MS, Oddis CV, Birder LA, Malinski T. β-Adrenergic regulation of constitutive nitric oxide synthase in cardiac myocytes. Am J Physiol Cell Physiol 273: C1371-C1377, 1997.
70. Kanai AJ, Pearce LL, Clemens PR, Birder LA, Vanbibber MM, Choi SY, De Groat WC, Peterson J. Identification of a neuronal nitric oxide synthase in isolated cardiac mitochondria using electrochemical detection. Proc Natl Acad Sci USA 98: 14126-14131, 2001.
71. Kato K, Giulivi C. Critical overview of mitochondrial nitric-oxide synthase. Front Biosci 11: 2725-2738, 2006.
72. Katori T, Donzelli S, Tocchetti CG, Miranda KM, Cormaci G, Thomas DD, Ketner EA, Lee MJ, Mancardi D, Wink DA, Kass DA, Paolocci N. Peroxynitrite and myocardial contractility: in vivo versus in vitro effects. Free Radic Biol Med 41: 1606-1618, 2006.
73. Kaye DM, Wiviott SD, Balligand JL, Simmons WW, Smith TW, Kelly RA. Frequency-dependent activation of a constitutive nitric oxide synthase and regulation of contractile function in adult rat ventricular myocytes. Circ Res 78: 217-224, 1996.
74. Koesling D, Friebe A. Structure-function relationships in NO-sensitive guanlylyl ciclase. In: Nitric Oxide: Biology and Pathobiology, edited by Ignarro LJ. New York: Academic, 2000, p. 369-379.
75. Koppenol WH, Moreno JJ, Pryor WA, Ischiropoulos H, Beckman JS. Peroxynitrite, a cloaked oxidant formed by nitric oxide and superoxide. Chem Res Toxicol 5: 834-842, 1992.
76. La Padula P, Costa LE. Effect of sustained hypobaric hypoxia during maturation and aging on rat myocardium. I. Mechanical activity. J Appl Physiol 98: 2363-2369, 2005.
77. La Padula P, Bustamante J, Czerniczyniec A, Costa LE. Time course of regression of the protection conferred by simulated high altitude to rat myocardium: correlation with mtNOS. J Appl Physiol 105: 951-957, 2008.
78. Lacza Z, Puskar M, Figueroa JP, Zhang J, Rajapakse N, Busija DW. Mitochondrial nitric oxide synthase is constitutively active and is functionally upregulated in hypoxia. Free Radic Biol Med 31: 1609-1615, 2001.
79. Lacza Z, Snipes JA, Zhang J, Horvath EM, Figueroa JP, Szabo C, Busija DW. Mitochondrial nitric oxide synthase is not eNOS, nNOS or iNOS. Free Radic Biol Med 35: 1217-1228, 2003.
80. Lacza Z, Pankotai E, Csordas A, Gero D, Kiss L, Horvath EM, Kollai M, Busija DW, Szabo C. Mitochondrial NO and reactive nitrogen species production: does mtNOS exist? Nitric Oxide 14: 162-168, 2006.
81. Layland J, Li JM, Shah AM. Role of cyclic GMP-dependent protein kinase in the contractile response to exogenous nitric oxide in rat cardiac myocytes. J Physiol 540: 457-467, 2002.
82. Leite AC, Oliveira HC, Utino FL, Garcia R, Alberici LC, Fernandes MP, Castilho RF, Vercesi AE. Mitochondria generated nitric oxide protects against permeability transition via formation of membrane protein S-nitrosothiols. Biochim Biophys Acta 1797: 1210-1216, 2010.
83. 2+ and its effects on energetics and redox balance in normal and failing heart. J Bioenerg Biomembr 41: 127-132, 2009.
84. 2within the hydrophobic interior of biological membranes. Proc Natl Acad Sci USA 95: 2175-2179, 1998.
85. Lopez-Figueroa MO, Caamano C, Morano MI, Ronn LC, Akil H, Watson SJ. Direct evidence of nitric oxide presence within mitochondria. Biochem Biophys Res Commun 272: 129-133, 2000.
86. Lyon AR, Joudrey PJ, Jin D, Nass RD, Aon MA, O'Rourke B, Akar FG. Optical imaging of mitochondrial function uncovers actively propagating waves of mitochondrial membrane potential collapse across intact heart. J Mol Cell Cardiol 49: 565-575, 2010.
87. Ma XL, Gao F, Lopez BL, Christopher TA, Vinten-Johansen J. Peroxynitrite, a two-edged sword in post-ischemic myocardial injurydichotomy of action in crystalloid-versus blood-perfused hearts. J Pharmacol Exp Ther 292: 912-920, 2000.
88. Makazan Z, Saini HK, Dhalla NS. Role of oxidative stress in alterations of mitochondrial function in ischemic-reperfused hearts. Am J Physiol Heart Circ Physiol 292: H1986-H1994, 2007.
89. 2+ and hypoxia. Studies in rat heart mitochondria. Amino Acids 22: 381-389, 2002.
90. Massion PB, Feron O, Dessy C, Balligand JL. Nitric oxide and cardiac function: ten years after, and continuing. Circ Res 93: 388-398, 2003.
91. Mihm MJ, Bauer JA. Peroxynitrite-induced inhibition and nitration of cardiac myofibrillar creatine kinase. Biochimie 84: 1013-1019, 2002.
92. Moncada S, Erusalimsky JD. Does nitric oxide modulate mitochondrial energy generation and apoptosis? Nat Rev Mol Cell Biol 3: 214-220, 2002.
93. Nadtochiy SM, Burwell LS, Ingraham CA, Spencer CM, Friedman AE, Pinkert CA, Brookes PS. In vivo cardioprotection by S-nitroso-2-mercaptopropionyl glycine. J Mol Cell Cardiol 46: 960-968, 2009.
94. Nagendran J, Michelakis ED. Mitochondrial NOS is upregulated in the hypoxic heart: implications for the function of the hypertrophied right ventricle. Am J Physiol Heart Circ Physiol 296: H1723-H1726, 2009.
95. Nazarewicz RR, Zenebe WJ, Parihar A, Larson SK, Alidema E, Choi J, Ghafourifar P. Tamoxifen induces oxidative stress and mitochondrial apoptosis via stimulating mitochondrial nitric oxide synthase. Cancer Res 67: 1282-1290, 2007.
96. Neckár J, Marková I, Novák F, Nováková O, Szárszoi O, Ost'ádal B, Kolár F. Increased expression and altered subcellular distribution of PKC-delta in chronically hypoxic rat myocardium: involvement in cardioprotection. Am J Physiol Heart Circ Physiol 288: H1566-H1572, 2005.
97. Nisoli E. Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science 310: 314-317, 2005.
98. Nohl H, Staniek K, Sobhian B, Bahrami S, Redl H, Kozlov AV. Mitochondria recycle nitrite back to the bioregulator nitric monoxide. Acta Biochim Pol 47: 913-921, 2000.
99. Nouette-Gaulain K, Malgat M, Rocher C, Savineau JP, Marthan R, Mazat JP, Sztark F. Time course of differential mitochondrial energy metabolism adaptation to chronic hypoxia in right and left ventricles. Cardiovasc Res 66: 132-140, 2005.
100. Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327: 524-526, 1987.
101. Palmer RM, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 333: 664-666, 1988.
102. Paolocci N, Ekelund UE, Isoda T, Ozaki M, Vandegaer K, Georgakopoulos D, Harrison RW, Kass DA, Hare JM. cGMP-independent inotropic effects of nitric oxide and peroxynitrite donors: potential role for nitrosylation. Am J Physiol Heart Circ Physiol 279: H1982-H1988, 2000.
103. Peralta JG, Finocchietto PV, Converso D, Schopfer F, Carreras MC, Poderoso JJ. Modulation of mitochondrial nitric oxide synthase and energy expenditure in rats during cold acclimation. Am J Physiol Heart Circ Physiol 284: H2375-H2383, 2003.
104. Persichini T, Mazzone V, Polticelli F, Moreno S, Venturini G, Clementi E, Colasanti M. Mitochondrial type I nitric oxide synthase physically interacts with cytochrome c oxidase. Neurosci Lett 384: 254-259, 2005.
105. Pinsky DJ, Patton S, Mesaros S, Brovkovych V, Kubaszewski E, Grunfeld S, Malinski T. Mechanical transduction of nitric oxide synthesis in the beating heart. Circ Res 81: 372-379, 1997.
106. Poderoso JJ, Carreras MC, Lisdero C, Riobo N, Schopfer F, Boveris A. Nitric oxide inhibits electron transfer and increases superoxide radical production in rat heart mitochondria and submitochondrial particles. Arch Biochem Biophys 328: 85-92, 1996.
107. Poderoso JJ, Peralta JG, Lisdero CL, Carreras MC, Radisic M, Schopfer F, Cadenas E, Boveris A. Nitric oxide regulates oxygen uptake and hydrogen peroxide release by the isolated beating rat heart. Am J Physiol Cell Physiol 274: C112-C119, 1998.
108. Prime TA, Blaikie FH, Evans C, Nadtochiy SM, James AM, Dahm CC, Vitturi DA, Patel RP, Hiley CR, Abakumova I, Requejo R, Chouchani ET, Hurd TR, Garvey JF, Taylor CT, Brookes PS, Smith RA, Murphy MP. A mitochondria-targeted S-nitrosothiol modulates respiration, nitrosates thiols, and protects against ischemia-reperfusion injury. Proc Natl Acad Sci USA 106: 10764-10769, 2009.
109. Δ/Δ mice). Brain Res Mol Brain Res 85: 13-23, 2000.
110. Radi R, Cassina A, Hodara R, Quijano C, Castro L. Peroxynitrite reactions and formation in mitochondria. Free Radic Biol Med 33: 1451-1464, 2002.
111. Rakhit RD, Mojet MH, Marber MS, Duchen MR. Mitochondria as targets for nitric oxide-induced protection during simulated ischemia and reoxygenation in isolated neonatal cardiomyocytes. Circulation 103: 2617-2623, 2001.
112. Rouet-Benzineb P, Eddahibi S, Raffestin B, Laplace M, Depond S, Adnot S, Crozatier B. Induction of cardiac nitric oxide synthase 2 in rats exposed to chronic hypoxia. J Mol Cell Cardiol 31: 1697-1708, 1999.
113. Saavedra-Molina A, Ramirez-Emiliano J, Clemente-Guerrero M, Perez-Vazquez V, Aguilera-Aguirre L, Gonzalez-Hernandez JC. Mitochondrial nitric oxide inhibits ATP synthesis. Effect of free calcium in rat heart. Amino Acids 24: 95-102, 2003.
114. Saavedra WF, Paolocci N, St John ME, Skaf MW, Stewart GC, Xie JS, Harrison RW, Zeichner J, Mudrick D, Marban E, Kass DA, Hare JM. Imbalance between xanthine oxidase and nitric oxide synthase signaling pathways underlies mechanoenergetic uncoupling in the failing heart. Circ Res 90: 297-304, 2002.
115. Scharfstein JS, Keaney JF Jr, Slivka A, Welch GN, Vita JA, Stamler JS, Loscalzo J. In vivo transfer of nitric oxide between a plasma protein-bound reservoir and low molecular weight thiols. J Clin Invest 94: 1432-1439, 1994.
116. Schild L, Reinheckel T, Reiser M, Horn TF, Wolf G, Augustin W. Nitric oxide produced in rat liver mitochondria causes oxidative stress and impairment of respiration after transient hypoxia. FASEB J 17: 2194-2201, 2003.
117. Shiva S, Sack MN, Greer JJ, Duranski M, Ringwood LA, Burwell L, Wang X, Macarthur PH, Shoja A, Raghavachari N, Calvert JW, Brookes PS, Lefer DJ, Gladwin MT. Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer. J Exp Med 204: 2089-2102, 2007.
118. Simon DI, Mullins ME, Jia L, Gaston B, Singel DJ, Stamler JS. Polynitrosylated proteins: characterization, bioactivity, and functional consequences. Proc Natl Acad Sci USA 93: 4736-4741, 1996.
119. Stamler JS, Lamas S, Fang FC. Nitrosylation: the prototypic redoxbased signaling mechanism. Cell 106: 675-683, 2001.
120. Steppan J, Ryoo S, Schuleri KH, Gregg C, Hasan RK, White AR, Bugaj LJ, Khan M, Santhanam L, Nyhan D, Shoukas AA, Hare JM, Berkowitz DE. Arginase modulates myocardial contractility by a nitric oxide synthase 1-dependent mechanism. Proc Natl Acad Sci USA 103: 4759-4764, 2006.
121. Sun J, Xin C, Eu JP, Stamler JS, Meissner G. Cysteine-3635 is responsible for skeletal muscle ryanodine receptor modulation by NO. Proc Natl Acad Sci USA 98: 11158-11162, 2001.
122. Tay YM, Lim KS, Sheu FS, Jenner A, Whiteman M, Wong KP, Halliwell B. Do mitochondria make nitric oxide? no? Free Radic Res 38: 591-599, 2004.
123. Ullrich R, Scherrer-Crosbie M, Bloch KD, Ichinose F, Nakajima H, Picard MH, Zapol WM, Quezado ZM. Congenital deficiency of nitric oxide synthase 2 protects against endotoxin-induced myocardial dysfunction in mice. Circulation 102: 1440-1446, 2000.
124. Valdez LB, Boveris A. Mitochondrial nitric oxide synthase, a voltagedependent enzyme, is responsible for nitric oxide diffusion to cytosol. Front Biosci 12: 1210-1219, 2007.
125. Valdez LB, Zaobornyj T, Boveris A. Functional activity of mitochondrial nitric oxide synthase. Methods Enzymol 396: 444-455, 2005.
126. Valdez LB, Zaobornyj T, Boveris A. Mitochondrial metabolic states and membrane potential modulate mtNOS activity. Biochim Biophys Acta 1757: 166-172, 2006.
127. Valdez LB, Zaobornyj T, Alvarez S, Bustamante J, Costa LE, Boveris A. Heart mitochondrial nitric oxide synthase. Effects of hypoxia and aging. Mol Aspects Med 25: 49-59, 2004.
128. Valdez LB, Zaobornyj T, Bombicino S, Iglesias DE, Boveris A, Donato M, D'Annunzio V, Buchholz B, Gelpi RJ. Complex I syndrome in myocardial stunning and the effect of adenosine. Free Radic Biol Med 51: 1203-1212, 2011.
129. Wang G, Liem DA, Vondriska TM, Honda HM, Korge P, Pantaleon DM, Qiao X, Wang Y, Weiss JN, Ping P. Nitric oxide donors protect murine myocardium against infarction via modulation of mitochondrial permeability transition. Am J Physiol Heart Circ Physiol 288: H1290-H1295, 2005.
130. Webb A, Bond R, Mclean P, Uppal R, Benjamin N, Ahluwalia A. Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage. Proc Natl Acad Sci USA 101: 13683-13688, 2004.
131. Wildhirt SM, Weismueller S, Schulze C, Conrad N, Kornberg A, Reichart B. Inducible nitric oxide synthase activation after ischemia/ reperfusion contributes to myocardial dysfunction and extent of infarct size in rabbits: evidence for a late phase of nitric oxide-mediated reperfusion injury. Cardiovasc Res 43: 698-711, 1999.
132. Wink DA, Mitchell JB. Chemical biology of nitric oxide: Insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide. Free Radic Biol Med 25: 434-456, 1998.
133. Wink DA, Cook JA, Kim SY, Vodovotz Y, Pacelli R, Krishna MC, Russo A, Mitchell JB, Jourd'heuil D, Miles AM, Grisham MB. Superoxide modulates the oxidation and nitrosation of thiols by nitric oxide-derived reactive intermediates. Chemical aspects involved in the balance between oxidative and nitrosative stress. J Biol Chem 272: 11147-11151, 1997.
134. Xie YW, Wolin MS. Role of nitric oxide and its interaction with superoxide in the suppression of cardiac muscle mitochondrial respiration. Involvement in response to hypoxia/reoxygenation. Circulation 94: 2580-2586, 1996.
135. Xu KY, Huso DL, Dawson TM, Bredt DS, Becker LC. Nitric oxide synthase in cardiac sarcoplasmic reticulum. Proc Natl Acad Sci USA 96: 657-662, 1999.
136. Yang B, Larson DF, Watson R. Age-related left ventricular function in the mouse: analysis based on in vivo pressure-volume relationships. Am J Physiol Heart Circ Physiol 277: H1906-H1913, 1999.
137. Zanella B, Calonghi N, Pagnotta E, Masotti L, Guarnieri C. Mitochondrial nitric oxide localization in H9c2 cells revealed by confocal microscopy. Biochem Biophys Res Commun 290: 1010-1014, 2002.
138. Zanella B, Giordano E, Muscari C, Zini M, Guarnieri C. Nitric oxide synthase activity in rat cardiac mitochondria. Basic Res Cardiol 99: 159-164, 2004.
139. Zaobornyj T, Valdez LB, La Padula P, Costa LE, Boveris A. Effect of sustained hypobaric hypoxia during maturation and aging on rat myocardium. II. mtNOS activity. J Appl Physiol 98: 2370-2375, 2005.
140. Zaobornyj T, Valdez LB, Iglesias DE, Gasco M, Gonzales GF, Boveris A. Mitochondrial nitric oxide metabolism during rat heart adaptation to high altitude: effect of sildenafil, L-NAME, and L-arginine treatments. Am J Physiol Heart Circ Physiol 296: H1741-H1747, 2009.
141. Zenebe WJ, Nazarewicz RR, Parihar MS, Ghafourifar P. Hypoxia/ reoxygenation of isolated rat heart mitochondria causes cytochrome c release and oxidative stress; evidence for involvement of mitochondrial nitric oxide synthase. J Mol Cell Cardiol 43: 411-419, 2007.
142. Ziolo MT, Bers DM. The real estate of NOS signaling: location, location, location. Circ Res 92: 1279-1281, 2003.
143. Ziolo MT, Kohr MJ, Wang H. Nitric oxide signaling and the regulation of myocardial function. J Mol Cell Cardiol 45: 625-632, 2008.
144. 2+ transients. Circulation 109: 1886-1891, 2004.
145. Zorov DB, Kobrinsky E, Juhaszova M, Sollott SJ. Examining intracellular organelle function using fluorescent probes: from animalcules to quantum dots. Circ Res 95: 239-252, 2004.
146. Zweier JL, Wang P, Samouilov A, Kuppusamy P. Enzyme-independent formation of nitric oxide in biological tissues. Nat Med 1: 804-809, 1995.