Mitochondrial complex I function modulates volatile anesthetic sensitivity in C. elegans
Open accessAbstract
Despite the widespread clinical use of volatile anesthetics, their mechanisms of action remain unknown [1-6]. An unbiased genetic screen in the nematode C. elegans for animals with altered volatile anesthetic sensitivity identified a mutant in a nuclear-encoded subunit of mitochondrial complex I [7,8]. This raised the question of whether mitochondrial dysfunction might be the primary mechanism by which volatile anesthetics act, rather than an untoward secondary effect [9,10]. We report here analysis of additional C. elegans mutations in orthologs of human genes that contribute to the formation of complex I, complex II, complex III, and coenzyme Q [11-14]. To further characterize the specific contribution of complex I, we generated four hypomorphic C. elegans mutants encoding different complex I subunits [15]. Our main finding is the identification of a clear correlation between complex I-dependent oxidative phosphorylation capacity and volatile anesthetic sensitivity. These extended data link a physiologic determinant of anesthetic action in a tractable animal model to similar clinical observations in children with mitochondrial myopathies [16]. This work is the first to specifically implicate complex I-dependent oxidative phosphorylation function as a primary mediator of volatile anesthetic effect.
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Mutations affecting complexes II-IV do not change anesthetic sensitivity.
“Mutations affecting complexes II-IV do not alter anesthetic sensitivity”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [92]
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- Authors
- Falk, M. J., Kayser, E.-B., Morgan, P. G., & Sedensky, M. M.
- Affiliations
- University Hospitals of Cleveland (US)
- Corresponding author
- Sedensky, Margaret M.
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2006-08
- Volume
- 16
- Issue
- 16
- Pages
- 1641-1645
- ISSN
- 0960-9822 (ISSN-L)
- PMC
- PMC3641903
- OpenAlex
- W2018676384
- Cited by
- 69
- References
- 31
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- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2578 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5k08dk073545-05)
- National Institute of General Medical Sciences (R01GM058881)
- National Institute of Diabetes and Digestive and Kidney Diseases (K08-DK073545, 1K08 DK 073545-01)
- National Center for Research Resources (K12RR023264)
- Topics
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Keywords
- mitochondrial complex I, volatile anesthetics, anesthetic sensitivity, oxidative phosphorylation, mitochondrial dysfunction, Caenorhabditis elegans, complex II, cytochrome bc1 complex, coenzyme Q10, hypomorphic mutants, mitochondrial myopathy
- MeSH terms
- Anesthetics, Animals, Genetic Testing, Halothane, Mitochondria, Mutation, Oxidative Phosphorylation, Caenorhabditis elegans, RNA Interference, Electron Transport Chain Complex Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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