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Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals.

Enzo Nisoli·Sestina Falcone·Cristina Tonello·Valeria Cozzi·Letizia Palomba·Mara Fiorani·Addolorata Pisconti·Silvia Brunelli·Annalisa Cardile·Maura Francolini·Orazio Cantoni·Michele O Carruba·Salvador Moncada·Emilio Clementi
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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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Adenosine TriphosphateAnimalsBrainCell LineCyclic GMPGlycolysisHumansKidneyMiceMice, KnockoutMitochondriaMitochondria, HeartMitochondria, LiverMitochondria, MuscleNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IINitric Oxide Synthase Type IIIOxygen ConsumptionPC12 CellsRatsTranscription, GeneticU937 CellsJournal ArticleResearch Support, Non-U.S. Gov't

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Enzo Nisoli, Sestina Falcone, Cristina Tonello, Valeria Cozzi, Letizia Palomba, Mara Fiorani, Addolorata Pisconti, Silvia Brunelli, Annalisa Cardile, Maura Francolini, Orazio Cantoni, Michele O Carruba, Salvador Moncada, Emilio Clementi. 2004-11-15. Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals.. https://doi.org/10.1073/pnas.0405432101

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