ArticleMolecular pharmacology2015
The mitochondrial complex V-associated large-conductance inner membrane current is regulated by cyclosporine and dexpramipexole.
Article in Molecular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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.
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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.
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Who cites it
23 citing papers in PubMed, 50 citations in OpenAlex.
- Reversing Mitochondrial Dysfunction in Optineurin E50K Glaucoma: A Metabolic Approach to Neuroprotection.Research square · 2026Article
- Study on the mechanism of Dexmedetomidine's effect on postoperative cognitive dysfunction in elderly people.Frontiers in physiology · 2025Review
- Article
- Review
- Identity, structure, and function of the mitochondrial permeability transition pore: controversies, consensus, recent advances, and future directions.Cell death and differentiation · 2023Review
- Molecular mechanisms and consequences of mitochondrial permeability transition.Nature reviews. Molecular cell biology · 2022Review
- Dexpramipexole Enhances KMolecular neurobiology · 2021Article
- Calcium influx through the mitochondrial calcium uniporter holocomplex, MCUJournal of molecular and cellular cardiology · 2021Review
- Natural products and other inhibitors of FEuropean journal of medicinal chemistry · 2020Review
- Neuroprotection induced by dexpramipexole delays disease progression in a mouse model of progressive multiple sclerosis.British journal of pharmacology · 2020Article
- ATP synthase c-subunit ring as the channel of mitochondrial permeability transition: Regulator of metabolism in development and degeneration.Journal of molecular and cellular cardiology · 2020Review
- Translational issues for mitoprotective agents as adjunct to reperfusion therapy in patients with ST-segment elevation myocardial infarction.Journal of cellular and molecular medicine · 2020Review
- Mitochondrial Membrane Intracellular Communication in Healthy and Diseased Myocardium.Frontiers in cell and developmental biology · 2020Review
- A mitochondrial megachannel resides in monomeric FNature communications · 2019Article
- Parkinson's disease protein DJ-1 regulates ATP synthase protein components to increase neuronal process outgrowth.Cell death & disease · 2019Article
- Dexpramipexole improves bioenergetics and outcome in experimental stroke.British journal of pharmacology · 2018Article
- Mitochondrial permeability transition pore: sensitivity to opening and mechanistic dependence on substrate availability.Scientific reports · 2017Article
- Identification of ER-000444793, a Cyclophilin D-independent inhibitor of mitochondrial permeability transition, using a high-throughput screen in cryopreserved mitochondria.Scientific reports · 2016Article
- The Dual Function of Reactive Oxygen/Nitrogen Species in Bioenergetics and Cell Death: The Role of ATP Synthase.Oxidative medicine and cellular longevity · 2016Review
- Pramipexole at a Low Dose Induces Beneficial Effect in the Harmaline-induced Model of Essential Tremor in Rats.CNS neuroscience & therapeutics · 2016Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Inefficiency of oxidative phosphorylation can result from futile leak conductance through the inner mitochondrial membrane. Stress or injury may exacerbate this leak conductance, putting cells, and particularly neurons, at risk of dysfunction and even death when energy demand exceeds cellular energy production. Using a novel method, we have recently described an ion conductance consistent with mitochondrial permeability transition pore (mPTP) within the c-subunit of the ATP synthase. Excitotoxicity, reactive oxygen species-producing stimuli, or elevated mitochondrial matrix calcium opens the channel, which is inhibited by cyclosporine A and ATP/ADP. Here we show that ATP and the neuroprotective drug dexpramipexole (DEX) inhibited an ion conductance consistent with this c-subunit channel (mPTP) in brain-derived submitochondrial vesicles (SMVs) enriched for F1FO ATP synthase (complex V). Treatment of SMVs with urea denatured extramembrane components of complex V, eliminated DEX- but not ATP-mediated current inhibition, and reduced binding of [(14)C]DEX. Direct effects of DEX on the synthesis and hydrolysis of ATP by complex V suggest that interaction of the compound with its target results in functional conformational changes in the enzyme complex. [(14)C]DEX bound specifically to purified recombinant b and oligomycin sensitivity-conferring protein subunits of the mitochondrial F1FO ATP synthase. Previous data indicate that DEX increased the efficiency of energy production in cells, including neurons. Taken together, these studies suggest that modulation of a complex V-associated inner mitochondrial membrane current is metabolically important and may represent an avenue for the development of new therapeutics for neurodegenerative disorders.
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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.