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Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals
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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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Type 2 diabetes, mitochondrial biology and the heart
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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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