ArticleCommunications biology2020
Bedaquiline inhibits the yeast and human mitochondrial ATP synthases.
Article in Communications biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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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.
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.
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Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
- Bedaquiline inhibits the ATP synthase leak channel and prevents glutamate-induced neuronal death.Biophysical reports · 2026Article
- Single-Mitochondrion ATP Profiling Directs Discovery of Targetable OXPHOS Dependency in Cancers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- SIR-2.3/SIRT4 loss enhances proteostasis and neuronal resilience via AMPK-induced autophagy in Huntington's disease models.Cell communication and signaling : CCS · 2026Article
- Bedaquiline inhibits the ATP synthase leak channel and prevents glutamate-induced neuronal death.bioRxiv : the preprint server for biology · 2026Article
- Investigation of mitochondrial inner membrane ion conductance by planar lipid bilayer electrophysiology.Frontiers in physiology · 2026Article
- Remission spectroscopy resolves the mechanism of action of bedaquiline within living mycobacteria.Nature communications · 2025Article
- Scaffold Hopping in Tuberculosis Drug Discovery: Principles, Applications, and Case Studies.Journal of medicinal chemistry · 2025Review
- Protein kinase G-a key regulator of pathogenesis in Mycobacterium tuberculosis infection.Archives of microbiology · 2025Review
- Synthesis and Structure-Activity Relationship (SAR) Studies on New 4-Aminoquinoline-Hydrazones and Isatin Hybrids as Promising Antibacterial Agents.Molecules (Basel, Switzerland) · 2024Article
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- Conformational ensemble of yeast ATP synthase at low pH reveals unique intermediates and plasticity in FNature structural & molecular biology · 2024Article
- Micro-nanoemulsion and nanoparticle-assisted drug delivery against drug-resistant tuberculosis: recent developments.Clinical microbiology reviews · 2023Review
- The mitochondrial ATP synthase is a negative regulator of the mitochondrial permeability transition pore.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Repurposing an Antioxidant to KillBiomolecules · 2023Article
- Mitochondrial dysfunction at the crossroad of cardiovascular diseases and cancer.Journal of translational medicine · 2023Review
- Inhibitors of ATP Synthase as New Antibacterial Candidates.Antibiotics (Basel, Switzerland) · 2023Review
- FInternational journal of molecular sciences · 2023Review
- Identification of 2-Aryl-Quinolone Inhibitors of CytochromeACS infectious diseases · 2023Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Bedaquiline (BDQ, Sirturo) has been approved to treat multidrug resistant forms of Mycobacterium tuberculosis. Prior studies suggested that BDQ was a selective inhibitor of the ATP synthase from M. tuberculosis. However, Sirturo treatment leads to an increased risk of cardiac arrhythmias and death, raising the concern that this adverse effect results from inhibition at a secondary site. Here we show that BDQ is a potent inhibitor of the yeast and human mitochondrial ATP synthases. Single-particle cryo-EM reveals that the site of BDQ inhibition partially overlaps with that of the inhibitor oligomycin. Molecular dynamics simulations indicate that the binding mode of BDQ to this site is similar to that previously seen for a mycobacterial enzyme, explaining the observed lack of selectivity. We propose that derivatives of BDQ ought to be made to increase its specificity toward the mycobacterial enzyme and thereby reduce the side effects for patients that are treated with Sirturo.
Indexed as
Identifiers
32814813PMC7438494W3072204830What 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.