Cited by 495Mitochondrial Function and PathologyAdipose Tissue and MetabolismAutophagy in Disease and Therapy

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Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals

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Nisoli, Enzo, Falcone, Sestina, Tonello, Cristina, Cozzi, Valeria, Palomba, Letizia, Fiorani, Mara, Pisconti, Addolorata, Brunelli, Silvia, Cardile, Annalisa, Francolini, Maura, Cantoni, Orazio, Carruba, Michele O., Moncada, Salvador, Clementi, Emilio·2004·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0405432101PMC PMC534517

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Abstract

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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Gambardella, J., Fiordelisi, A., Cerasuolo, F. A., Buonaiuto, A., Avvisato, R., Viti, A., Sommella, E., Campiglia, P., D’Argenio, V., Prevete, N., et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.118183
BindingDB Entry 50043230: Effects of (-)-epicatechin and derivatives on nitric oxide mediated induction of mitochondrial proteins.
BindingDB (2014) · UC San Diego · doi:10.7270/q2p84d93
Investigating the role of nitric oxide clones in cardiovascular conditions
Arif, S. (2014) · University of Birmingham Institutional Research Archive (University of Birmingham)

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: Nisoli, Enzo
Falcone, Sestina
Palomba, Letizia
Fiorani, Mara
Pisconti, Addolorata
Brunelli, Silvia
Francolini, Maura
Cantoni, Orazio
Carruba, Michele O.
Moncada, Salvador
Clementi, Emilio
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
DOI: 10.1073/pnas.0405432101
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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Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals

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