ArticleAnesthesia and analgesia2011
Isoflurane selectively inhibits distal mitochondrial complex I in Caenorhabditis elegans.
Article in Anesthesia and analgesia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 38 citations in OpenAlex.
- Stress Pathways Induced by Volatile Anesthetics and Failure of Preconditioning in a Mitochondrial Complex I Mutant.Anesthesiology · 2024Article
- A primordial target: Mitochondria mediate both primary and collateral anesthetic effects of volatile anesthetics.Experimental biology and medicine (Maywood, N.J.) · 2023Review
- The effects of general anesthetics on mitochondrial structure and function in the developing brain.Frontiers in neurology · 2023Review
- Metabolomic profiling reveals muscle metabolic changes following iliac arteriovenous fistula creation in mice.American journal of physiology. Renal physiology · 2022Article
- Review
- Isoflurane inhibition of endocytosis is an anesthetic mechanism of action.Current biology : CB · 2022Article
- Article
- Dynamic Variations in Brain Glycogen are Involved in Modulating Isoflurane Anesthesia in Mice.Neuroscience bulletin · 2020Article
- Mitochondrial Complex I Mutations Predispose Drosophila to Isoflurane Neurotoxicity.Anesthesiology · 2020Article
- Trichloroethylene, a ubiquitous environmental contaminant in the risk for Parkinson's disease.Environmental science. Processes & impacts · 2020Article
- Mitochondrial Function in Astrocytes Is Essential for Normal Emergence from Anesthesia in Mice.Anesthesiology · 2019Article
- Relevance of experimental paradigms of anesthesia induced neurotoxicity in the mouse.PloS one · 2019Article
- Anesthetics Have Different Effects on the Electrocorticographic Spectra of Wild-type and Mitochondrial Mutant Mice.Anesthesiology · 2018Article
- Isoflurane disrupts excitatory neurotransmitter dynamics via inhibition of mitochondrial complex I.British journal of anaesthesia · 2018Article
- Persistent mitoKMolecular neurobiology · 2017Article
- Regional knockdown of NDUFS4 implicates a thalamocortical circuit mediating anesthetic sensitivity.PloS one · 2017Article
- Reactive Oxygen Species-mediated Loss of Phenotype of Parvalbumin Interneurons Contributes to Long-term Cognitive Impairments After Repeated Neonatal Ketamine Exposures.Neurotoxicity research · 2016Article
- Glutamatergic Neurotransmission Links Sensitivity to Volatile Anesthetics with Mitochondrial Function.Current biology : CB · 2016Article
- Chemical Conditioning as an Approach to Ischemic Stroke Tolerance: Mitochondria as the Target.International journal of molecular sciences · 2016Review
- Increased mitochondrial ATP production capacity in brain of healthy mice and a mouse model of isolated complex I deficiency after isoflurane anesthesia.Journal of inherited metabolic disease · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundComplex I of the electron transport chain (ETC) is a possible target of volatile anesthetics (VAs). Complex I enzymatic activities are inhibited by VAs, and dysfunction of complex I can lead to hypersensitivity to VAs in worms and in people. Mutant analysis in Caenorhabditis (C.) elegans suggests that VAs may specifically interfere with complex I function at the binding site for its substrate ubiquinone. We hypothesized that isoflurane inhibits electron transport by competing with ubiquinone for binding to complex I.
methodsWildtype and mutant C. elegans were used to study the effects of isoflurane on isolated mitochondria. Enzymatic activities of the ETC were assayed and dose-response curves determined using established techniques. Two-dimensional native gels of mitochondrial proteins were performed after exposure of mitochondria to isoflurane.
resultsComplex I is the most sensitive component of the ETC to isoflurane inhibition; however, the proximal portion of complex I (the flavoprotein) is relatively insensitive to isoflurane. Isoflurane and quinone do not compete for a common binding site on complex I. The absolute rate of complex I enzymatic activity in vitro does not predict immobilization of the animal by isoflurane. Isoflurane had no measurable effect on stability of mitochondrial supercomplexes. Reduction of ubiquinone by complex I displayed positive cooperative kinetics not disrupted by isoflurane.
conclusionsIsoflurane directly inhibits complex I at a site distal to the flavoprotein subcomplex. However, we have excluded our original hypothesis that isoflurane and ubiquinone compete for a common hydrophobic binding site on complex I. In addition, immobilization of the nematode by isoflurane is not due to limiting absolute amounts of complex I electron transport as measured in isolated mitochondria.
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.