ReviewJournal of bioenergetics and biomembranes2011
Mammalian NADH:ubiquinone oxidoreductase (Complex I) and nicotinamide nucleotide transhydrogenase (Nnt) together regulate the mitochondrial production of H₂O₂--implications for their role in disease, especially cancer.
Review in Journal of bioenergetics and biomembranes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Pharmacological potential of Chinese botanical drugs in managing chronic kidney disease by targeting mitochondrial quality control.Frontiers in pharmacology · 2025Review
- Mitochondrial quality control in human health and disease.Military Medical Research · 2024Review
- Obesogens: a unifying theory for the global rise in obesity.International journal of obesity (2005) · 2024Review
- Reactive oxygen species: role in obesity and mitochondrial energy efficiency.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Microbiome-derived cobalamin and succinyl-CoA as biomarkers for improved screening of anal cancer.Nature medicine · 2023Article
- Mitochondria ROS and mitophagy in acute kidney injury.Autophagy · 2023Article
- Review
- B2 SINE Copies Serve as a Transposable Boundary of DNA Methylation and Histone Modifications in the Mouse.Molecular biology and evolution · 2021Article
- Generation of Reactive Oxygen Species by Mitochondria.Antioxidants (Basel, Switzerland) · 2021Review
- Decomposing the Mechanism of Qishen Granules in the Treatment of Heart Failure by a Quantitative Pathway Analysis Method.Molecules (Basel, Switzerland) · 2018Article
- Proton-Translocating Nicotinamide Nucleotide Transhydrogenase: A Structural Perspective.Frontiers in physiology · 2017Review
- The Role of Metformin in Controlling Oxidative Stress in Muscle of Diabetic Rats.Oxidative medicine and cellular longevity · 2016Article
- Review
- Downregulation of NDUFB6 due to 9p24.1-p13.3 loss is implicated in metastatic clear cell renal cell carcinoma.Cancer medicine · 2015Article
- A review on the role of quinones in renal disorders.SpringerPlus · 2013Article
- Glutamate dehydrogenase contributes to leucine sensing in the regulation of autophagy.Autophagy · 2013Article
- The Role of Mitochondrial NADPH-Dependent Isocitrate Dehydrogenase in Cancer Cells.International journal of cell biology · 2012Article
- Nicotinamide, NAD(P)(H), and Methyl-Group Homeostasis Evolved and Became a Determinant of Ageing Diseases: Hypotheses and Lessons from Pellagra.Current gerontology and geriatrics research · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mammalian NADH:ubiquinone oxidoreductase (Complex I) in the mitochondrial inner membrane catalyzes the oxidation of NADH in the matrix. Excess NADH reduces nine of the ten prosthetic groups of the enzyme in bovine-heart submitochondrial particles with a rate of at least 3,300 s⁻¹. This results in an overall NADH→O₂ rate of ca. 150 s⁻¹. It has long been known that the bovine enzyme also has a specific reaction site for NADPH. At neutral pH excess NADPH reduces only three to four of the prosthetic groups in Complex I with a rate of 40 s⁻¹ at 22 °C. The reducing equivalents remain essentially locked in the enzyme because the overall NADPH→O₂ rate (1.4 s⁻¹) is negligible. The physiological significance of the reaction with NADPH is still unclear. A number of recent developments has revived our thinking about this enigma. We hypothesize that Complex I and the Δp-driven nicotinamide nucleotide transhydrogenase (Nnt) co-operate in an energy-dependent attenuation of the hydrogen-peroxide generation by Complex I. This co-operation is thought to be mediated by the NADPH/NADP⁺ ratio in the vicinity of the NADPH site of Complex I. It is proposed that the specific H₂O₂ production by Complex I, and the attenuation of it, is of importance for apoptosis, autophagy and the survival mechanism of a number of cancers. Verification of this hypothesis may contribute to a better understanding of the regulation of these processes.
Indexed as
Identifiers
What OpenQuestion holds
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.