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Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals
Open accessAbstract
We recently found that long-term exposure to nitric oxide (NO) triggers mitochondrial biogenesis in mammalian cells and tissues by activation of guanylate cyclase and generation of cGMP. Here, we report that the NO/cGMP-dependent mitochondrial biogenesis is associated with enhanced coupled respiration and content of ATP in U937, L6, and PC12 cells. The observed increase in ATP content depended entirely on oxidative phosphorylation, because ATP formation by glycolysis was unchanged. Brain, kidney, liver, heart, and gastrocnemius muscle from endothelial NO synthase null mutant mice displayed markedly reduced mitochondrial content associated with significantly lower oxygen consumption and ATP content. In these tissues, ultrastructural analyses revealed significantly smaller mitochondria. Furthermore, a significant reduction in the number of mitochondria was observed in the subsarcolemmal region of the gastrocnemius muscle. We conclude that NO/cGMP stimulates mitochondrial biogenesis, both in vitro and in vivo, and that this stimulation is associated with increased mitochondrial function, resulting in enhanced formation of ATP.
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“Chronic exposure to relatively high levels of NO results in mitochondrial biogenesis [113-115], which could reprogram a cell or tissue to have a higher metabolic capacity.”
From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [115]
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Cites
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425
Wu, Z., Puigserver, P., Andersson, U., Zhang, C., Adelmant, G., Mootha, V., Troy, A., Cinti, S., Lowell, B., Scarpulla, R. C., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)80611-x · Cited by 4,139
A Cold-Inducible Coactivator of Nuclear Receptors Linked to Adaptive Thermogenesis
Puigserver, P., Wu, Z., Park, C. W., Graves, R., Wright, M., & Spiegelman, B. M. (1998) · Cell · doi:10.1016/s0092-8674(00)81410-5 · Cited by 3,864
Mitochondrial diseases in man and mouse
Wallace, D. C. (1999) · Science · doi:10.1126/science.283.5407.1482 · Cited by 3,060
Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres
Lin, J., Wu, H., Tarr, P. T., Zhang, C.-Y., Wu, Z., Boss, O., Michael, L. F., Puigserver, P., Isotani, E., Olson, E. N., et al. (2002) · Nature · doi:10.1038/nature00904 · Cited by 2,546
Red Cell Metabolism: A Manual of Biochemical Methods.
(1971) · Annals of Internal Medicine · doi:10.7326/0003-4819-75-6-985_1 · Cited by 2,327
Hypertension in mice lacking the gene for endothelial nitric oxide synthase
Huang, P. L., Huang, Z., Mashimo, H., Bloch, K. D., Moskowitz, M. A., Bevan, J. A., & Fishman, M. C. (1995) · Nature · doi:10.1038/377239a0 · Cited by 2,070
Patti, M. E., Butte, A. J., Crunkhorn, S., Cusi, K., Berria, R., Kashyap, S., Miyazaki, Y., Kohane, I., Costello, M., Saccone, R., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1032913100 · Cited by 1,952
Stuehr, D. J., & Nathan, C. F. (1989) · The Journal of Experimental Medicine · doi:10.1084/jem.169.5.1543 · Cited by 1,744
Peroxisome proliferator–activated receptor γ coactivator-1 promotes cardiac mitochondrial biogenesis
Lehman, J. J., Barger, P. M., Kovacs, A., Saffitz, J. E., Medeiros, D. M., & Kelly, D. P. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10268 · Cited by 1,285
Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide
Nisoli, E., Clementi, E., Paolucci, C., Cozzi, V., Tonello, C., Sciorati, C., Bracale, R., Valerio, A., Francolini, M., Moncada, S., et al. (2003) · Science · doi:10.1126/science.1079368 · Cited by 1,243
Self-citationCleeter, M. W. J., Cooper, J. M., Darley-Usmar, V. M., Moncada, S., & Schapira, A. H. V. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)00424-2 · Cited by 1,241
Self-citationPhysiology of Nitric Oxide in Skeletal Muscle
Stamler, J. S., & Meissner, G. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.1.209 · Cited by 1,080
Estimation of surface area from vertical sections
Baddeley, A. J., Gundersen, H. J. G., & Cruz-Orive, L. M. (1986) · Journal of Microscopy · doi:10.1111/j.1365-2818.1986.tb04282.x · Cited by 1,057
Brown, G. C., & Cooper, C. E. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)01290-3 · Cited by 1,055
Bereiter‐Hahn, J., & Vöth, M. (1994) · Microscopy Research and Technique · doi:10.1002/jemt.1070270303 · Cited by 900
Nitric Oxide: Pathophysiological Mechanisms
Gross, S. S., & Wolin, M. S. (1995) · Annual Review of Physiology · doi:10.1146/annurev.ph.57.030195.003513 · Cited by 888
Clementi, E., Brown, G. C., Feelisch, M., & Moncada, S. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7631 · Cited by 863
Self-citationMitofusin-2 Determines Mitochondrial Network Architecture and Mitochondrial Metabolism
Bach, D., Pich, S., Soriano, F. X., Vega, N., Baumgartner, B., Oriola, J., Daugaard, J. R., Lloberas, J., Camps, M., Zierath, J. R., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212754200 · Cited by 832
Virbasius, J. V., & Scarpulla, R. C. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.4.1309 · Cited by 819
Does nitric oxide modulate mitochondrial energy generation and apoptosis?
Moncada, S., & Erusalimsky, J. D. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm762 · Cited by 794
Self-citationMolecular mechanisms and therapeutic strategies related to nitric oxide
Moncada, S., & Higgs, E. A. (1995) · The FASEB Journal · doi:10.1096/fasebj.9.13.7557022 · Cited by 776
Self-citationRedistribution of Intracellular Oxygen in Hypoxia by Nitric Oxide: Effect on HIF1α
Hagen, T., Taylor, C. T., Lam, F., & Moncada, S. (2003) · Science · doi:10.1126/science.1088805 · Cited by 704
Self-citationKopecky, J., Clarke, G., Enerbäck, S., Spiegelman, B., & Kozak, L. P. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118363 · Cited by 553
NO-independent regulatory site on soluble guanylate cyclase
Stasch, J., Becker, E. M., Alonso‐Alija, C., Apeler, H., Dembowsky, K., Feurer, A., Gerzer, R., Minuth, T., Perzborn, E., Pleiß, U., et al. (2001) · Nature · doi:10.1038/35065611 · Cited by 546
Almeida, Á., Moncada, S., & Bolaños, J. P. (2003) · Nature Cell Biology · doi:10.1038/ncb1080 · Cited by 481
Self-citationAcquirement of brown fat cell features by human white adipocytes
Tiraby, C., Tavernier, G., Lefort, C., Larrouy, D., Bouillaud, F., Ricquier, D., & Langin, D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305235200 · Cited by 474
Aerobic glycolysis by proliferating cells: a protective strategy against reactive oxygen species 1
Brand, K. A., & Hermfisse, U. (1997) · The FASEB Journal · doi:10.1096/fasebj.11.5.9141507 · Cited by 401
Effect of exogenous and endogenous nitric oxide on mitochondrial respiration of rat hepatocytes
Stadler, J., Billiar, T. R., CURRAN, R. D., Stuehr, D. J., Ochoa, J. B., & Simmons, R. L. (1991) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1991.260.5.c910 · Cited by 396
Beltrán, B., Mathur, A., Duchen, M. R., Erusalimsky, J. D., & Moncada, S. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.26.14602 · Cited by 395
Self-citationPerspectives on Oxygen Sensing
Semenza, G. L. (1999) · Cell · doi:10.1016/s0092-8674(00)81957-1 · Cited by 385
Stocchi, V., Cucchiarini, L., Magnani, M., Chiarantini, L., Palma, P., & Crescentini, G. (1985) · Analytical Biochemistry · doi:10.1016/0003-2697(85)90405-1 · Cited by 346
Nitric Oxide Potently and Reversibly Deenergizes Mitochondria at Low Oxygen Tension
Schweizer, M., & Richter, C. (1994) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1994.2441 · Cited by 331
On the mechanism by which vascular endothelial cells regulate their oxygen consumption
Clementi, E., Brown, G. C., Foxwell, N., & Moncada, S. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.4.1559 · Cited by 296
Self-citationCogswell, A. M., Stevens, R. J., & Hood, D. A. (1993) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1993.264.2.c383 · Cited by 286
Populations of rat skeletal muscle mitochondria after exercise and immobilization.
Krieger, D. A., Tate, C. A., McMillin-Wood, J., & Booth, F. W. (1980) · Journal of Applied Physiology · doi:10.1152/jappl.1980.48.1.23 · Cited by 212
Oxidative stress and S‐nitrosylation of proteins in cells
Beltrán, B., Orsi, A., Clementi, E., & Moncada, S. (2000) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0703147 · Cited by 196
Self-citationMitochondrial biogenesis during skeletal muscle regeneration
Duguez, S., Féasson, L., Denis, C., & Freyssenet, D. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00343.2001 · Cited by 183
Clementi, E., Scheer, H., Zacchetti, D., Fasolato, C., Pozzan, T., & Meldolesi, J. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)45858-9 · Cited by 169
Self-citationPlasticity of Skeletal Muscle Mitochondria in Response to Contractile Activity
Adhihetty, P. J., Irrcher, I., Joseph, A., Ljubicic, V., & Hood, D. A. (2003) · Experimental Physiology · doi:10.1113/eph8802505 · Cited by 165
Burgaud, J., Ongini, E., & Soldato, P. D. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb04080.x · Cited by 109
Nadai, C. D., Sestili, P., Cantoni, O., Lièvremont, J.-P., Sciorati, C., Barsacchi, R., Moncada, S., Meldolesi, J., & Clementi, E. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.070062397 · Cited by 109
Self-citationChapter 1 Isolation and subfractionation of mitochondria from animal cells and tissue culture lines
Pallotti, F., & Lenaz, G. (2001) · Methods in cell biology · doi:10.1016/s0091-679x(01)65002-7 · Cited by 96
Paolucci, C., Rovere, P. Q., Nadai, C. D., Manfredi, A. A., & Clementi, E. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000511200 · Cited by 53
Self-citationMomken, I., Fortin, D., Serrurier, B., Bigard, X. A., Ventura‐Clapier, R., & Veksler, V. (2002) · Biochemical Journal · doi:10.1042/bj20020591 · Cited by 41
Nakane, M. (2003) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2003.131 · Cited by 39
Roussel, D., Lhenry, F., Ecochard, L., SEMPORE, B., Rouanet, J., & Favier, R. J. M. (2000) · Biochemical Journal · doi:10.1042/bj3500547 · Cited by 30
Mitochondria in heart ischaemia and aging
Hansford, R. G., Tsuchiya, N., & Pepe, S. (1999) · Biochemical Society Symposia · doi:10.1042/bss0660141 · Cited by 25
Raichman, M., Panzeri, C., Clementi, E., Papazafiri, P., Eckley, D. M., Clegg, D., Villa, A., & Meldolesi, J. (1995) · The Journal of Cell Biology · doi:10.1083/jcb.128.3.341 · Cited by 21
Self-citationNitric oxide mediates brain mitochondrial maturation immediately after birth
Almeida, Á., Bolaños, J. P., & Medina, J. M. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00628-6 · Cited by 14
Effects of endogenous nitric oxide in activation of group IV muscle afferents
Arbogast, S., Darques, J. L., Brégeon, F., & Jammes, Y. (2001) · Muscle & Nerve · doi:10.1002/1097-4598(200102)24:2 · Cited by 9
Research works printed but not linked: 2
- Duguez, S., Feasson, L., Denis, C. & Freyssenet, D. (2002) Am. J. Physiol. 282, E802–E809.
- Nakane, M. (2003) Clin. Chem. Lab. Med. 41, 865–870.12940510
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Scarpulla, R. C. (2008) · Physiological Reviews · doi:10.1152/physrev.00025.2007 · Cited by 1,666
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Bhargava, P., & Schnellmann, R. G. (2017) · Nature Reviews Nephrology · doi:10.1038/nrneph.2017.107 · Cited by 1,391
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Metadata
- Authors
- Nisoli, E., Falcone, S., Tonello, C., Cozzi, V., Palomba, L., Fiorani, M., Pisconti, A., Brunelli, S., Cardile, A., Francolini, M., Cantoni, O., Carruba, M. O., Moncada, S., & Clementi, E.
- Affiliations
- University of Milan (IT)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2004-11-15
- Volume
- 101
- Issue
- 47
- Pages
- 16507-16512
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC534517
- OpenAlex
- W2116642215
- Cited by
- 495
- References
- 51
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 12 · 2023: 10 · 2022: 12 · 2021: 16 · 2020: 27 · 2019: 25 · 2018: 21 · 2017: 20 · 2016: 17 · 2015: 25 · 2014: 48 · 2013: 24 · 2012: 36
- FWCI
- 9.02
- Type
- journal article
- Language
- en
- Update notices
- correction (2005-04-12)
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- CINECA IRIS Institutional Research information system (University of Urbino) (submittedVersion)
- Funders
- Ministero della Salute
- Associazione Italiana per la Ricerca sul Cancro
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- mitochondrial biogenesis, nitric oxide, cGMP signaling, guanylate cyclase, oxidative phosphorylation, ATP production, coupled respiration, endothelial nitric oxide synthase, mitochondrial ultrastructure, muscle mitochondria, oxygen consumption
- MeSH terms
- Adenosine Triphosphate, Animals, Brain, Cell Line, Glycolysis, Cyclic GMP, Humans, Kidney, Mitochondria, Mitochondria, Heart, Mitochondria, Liver, Mitochondria, Muscle, Nitric Oxide, Oxygen Consumption, Transcription, Genetic, PC12 Cells, Mice, Knockout, Nitric Oxide Synthase, U937 Cells, Mice, Rats, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III
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