ArticleThe Journal of biological chemistry2014
Nitrite reductase and nitric-oxide synthase activity of the mitochondrial molybdopterin enzymes mARC1 and mARC2.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
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Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 170 citations in OpenAlex.
- Protective role of nitric oxide donors on endothelium in ischemia-reperfusion injury: a meta-analysis of randomized controlled trials.BMC anesthesiology · 2023Pooled it
- Effects of Oral Sodium Nitrite on Blood Pressure, Insulin Sensitivity, and Intima-Media Arterial Thickening in Adults With Hypertension and Metabolic Syndrome.Hypertension (Dallas, Tex. : 1979) · 2020Trial
- Structure and function of periplasmic nitrate reductase.Biochemical Society transactions · 2026Review
- Bovine xanthine oxidase electrocatalysis: substrate oxidation and its role in nitrite reduction.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2026Article
- Influence of exercise training on nitric oxide pathways and their physiological effects.Redox biology · 2026Review
- Loss of Mtarc1 Protects Against Steatotic Liver Disease in Mice.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Human genetics of metabolic dysfunction-associated steatotic liver disease: from variants to cause to precision treatment.The Journal of clinical investigation · 2025Review
- Second-Coordination-Sphere Effects Reveal Electronic Structure Differences between the Mitochondrial Amidoxime Reducing Component and Sulfite Oxidase.Inorganic chemistry · 2024Article
- Skeletal Muscle, Skin, and Bone as Three Major Nitrate Reservoirs in Mammals: Chemiluminescence andNutrients · 2024Article
- Melatonin-Nitric Oxide Crosstalk in Plants and the Prospects of NOMela as a Nitric Oxide Donor.International journal of molecular sciences · 2024Review
- Facilitating Nitrite-Derived S-Nitrosothiol Formation in the Upper Gastrointestinal Tract in the Therapy of Cardiovascular Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- A patient-based iPSC-derived hepatocyte model of alcohol-associated cirrhosis reveals bioenergetic insights into disease pathogenesis.Nature communications · 2024Article
- Liver-specific mitochondrial amidoxime-reducing component 1 (Mtarc1) knockdown protects the liver from diet-induced MASH in multiple mouse models.Hepatology communications · 2024Article
- Exploring the Impact of Alternative Sources of Dietary Nitrate Supplementation on Exercise Performance.International journal of molecular sciences · 2024Review
- Divergent role of Mitochondrial Amidoxime Reducing Component 1 (MARC1) in human and mouse.PLoS genetics · 2024Article
- The Cardioprotective Role of Nitrate-Rich Vegetables.Foods (Basel, Switzerland) · 2024Review
- Astrocytes produce nitric oxide via nitrite reduction in mitochondria to regulate cerebral blood flow during brain hypoxia.Cell reports · 2023Article
- Advancing Our Understanding of Pyranopterin-Dithiolene Contributions to Moco Enzyme Catalysis.Molecules (Basel, Switzerland) · 2023Review
- Bringing Nitric Oxide to the Molybdenum World-A Personal Perspective.Molecules (Basel, Switzerland) · 2023Review
- Does the Micronutrient Molybdenum Have a Role in Gestational Complications and Placental Health?Nutrients · 2023Review
15 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Mitochondrial amidoxime reducing component (mARC) proteins are molybdopterin-containing enzymes of unclear physiological function. Both human isoforms mARC-1 and mARC-2 are able to catalyze the reduction of nitrite when they are in the reduced form. Moreover, our results indicate that mARC can generate nitric oxide (NO) from nitrite when forming an electron transfer chain with NADH, cytochrome b5, and NADH-dependent cytochrome b5 reductase. The rate of NO formation increases almost 3-fold when pH was lowered from 7.5 to 6.5. To determine if nitrite reduction is catalyzed by molybdenum in the active site of mARC-1, we mutated the putative active site cysteine residue (Cys-273), known to coordinate molybdenum binding. NO formation was abolished by the C273A mutation in mARC-1. Supplementation of transformed Escherichia coli with tungsten facilitated the replacement of molybdenum in recombinant mARC-1 and abolished NO formation. Therefore, we conclude that human mARC-1 and mARC-2 are capable of catalyzing reduction of nitrite to NO through reaction with its molybdenum cofactor. Finally, expression of mARC-1 in HEK cells using a lentivirus vector was used to confirm cellular nitrite reduction to NO. A comparison of NO formation profiles between mARC and xanthine oxidase reveals similar Kcat and Vmax values but more sustained NO formation from mARC, possibly because it is not vulnerable to autoinhibition via molybdenum desulfuration. The reduction of nitrite by mARC in the mitochondria may represent a new signaling pathway for NADH-dependent hypoxic NO production.
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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.