ArticleFree radical biology & medicine2012
Nitrite activates AMP kinase to stimulate mitochondrial biogenesis independent of soluble guanylate cyclase.
Article in Free radical biology & medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 61 citations in OpenAlex.
- Investigation of the effect of nitrate and L-arginine intake on aerobic, anaerobic performance, balance, agility, and recovery in elite taekwondo athletes.Journal of the International Society of Sports Nutrition · 2025Trial
- Preworkout dietary nitrate magnifies training-induced benefits to physical function in late postmenopausal women: a randomized pilot study.American journal of physiology. Regulatory, integrative and comparative physiology · 2024Trial
- Triphenylphosphonium compounds preferentially inhibit long-chain fatty acid oxidation in cardiac mitochondria.Research square · 2026Article
- Nitrite increases mitofusin-1 levels to inhibit vascular smooth muscle cell proliferation and prevent intimal hyperplasia.Redox biology · 2026Article
- Exercise Training Decreases Nitrite Concentration in the Heart and Locomotory Muscles of Rats Without Changing the Muscle Nitrate Content.Journal of the American Heart Association · 2024Article
- Orally administered sodium nitrite prevents the increased α-1 adrenergic vasoconstriction induced by hypertension and promotes the S-nitrosylation of calcium/calmodulin-dependent protein kinase II.Biochemical pharmacology · 2023Article
- Dietary nitrate attenuates high-fat diet-induced obesity via mechanisms involving higher adipocyte respiration and alterations in inflammatory status.Redox biology · 2020Article
- Treatment with Nitrate, but Not Nitrite, Lowers the Oxygen Cost of Exercise and Decreases Glycolytic Intermediates While Increasing Fatty Acid Metabolites in Exercised Zebrafish.The Journal of nutrition · 2019Article
- Electrophilic nitro-oleic acid reverses obesity-induced hepatic steatosis.Redox biology · 2019Article
- Redox control of vascular smooth muscle cell function and plasticity.Laboratory investigation; a journal of technical methods and pathology · 2018Review
- Differential mitochondrial dinitrosyliron complex formation by nitrite and nitric oxide.Redox biology · 2018Article
- Hydrogen sulfide regulates cardiac mitochondrial biogenesis via the activation of AMPK.Journal of molecular and cellular cardiology · 2018Article
- Influence of dietary nitrate supplementation on physiological and muscle metabolic adaptations to sprint interval training.Journal of applied physiology (Bethesda, Md. : 1985) · 2017Article
- Article
- Sodium nitrite attenuates MMP-9 production by endothelial cells and may explain similar effects of atorvastatin.Naunyn-Schmiedeberg's archives of pharmacology · 2016Article
- Nitrate-containing beetroot enhances myocyte metabolism and mitochondrial content.Journal of traditional and complementary medicine · 2016Article
- Nitrate/Nitrite as Critical Mediators to Limit Oxidative Injury and Inflammation.Antioxidants & redox signaling · 2015Review
- Pharmacokinetic, partial pharmacodynamic and initial safety analysis of (-)-epicatechin in healthy volunteers.Food & function · 2015Article
- PINK1 deficiency impairs mitochondrial homeostasis and promotes lung fibrosis.The Journal of clinical investigation · 2015Article
- On the mechanism by which dietary nitrate improves human skeletal muscle function.Frontiers in physiology · 2015Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Nitrite, a dietary constituent and endogenous signaling molecule, mediates a number of physiological responses including modulation of ischemia/reperfusion injury, glucose tolerance, and vascular remodeling. Although the exact molecular mechanisms underlying nitrite's actions are unknown, the current paradigm suggests that these effects depend on the hypoxic reduction of nitrite to nitric oxide (NO). Mitochondrial biogenesis is a fundamental mechanism of cellular adaptation and repair. However, the effect of nitrite on mitochondrial number has not been explored. Herein, we report that nitrite stimulates mitochondrial biogenesis through a mechanism distinct from that of NO. We demonstrate that nitrite significantly increases cellular mitochondrial number by augmenting the activity of adenylate kinase, resulting in AMP kinase phosphorylation, downstream activation of sirtuin-1, and deacetylation of PGC1α, the master regulator of mitochondrial biogenesis. Unlike NO, nitrite-mediated biogenesis does not require the activation of soluble guanylate cyclase and results in the synthesis of more functionally efficient mitochondria. Further, we provide evidence that nitrite mediates biogenesis in vivo. In a rat model of carotid injury, 2 weeks of continuous oral nitrite treatment postinjury prevented the hyperproliferative response of smooth muscle cells. This protection was accompanied by a nitrite-dependent upregulation of PGC1α and increased mitochondrial number in the injured artery. These data are the first to demonstrate that nitrite mediates differential signaling compared to NO. They show that nitrite is a versatile regulator of mitochondrial function and number both in vivo and in vitro and suggest that nitrite-mediated biogenesis may play a protective role in the setting of vascular injury.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.