Evidence map›Paper›PMID 34849584›Full record

ReviewBrain : a journal of neurology2022

Ndufs4 knockout mouse models of Leigh syndrome: pathophysiology and intervention.

Melissa A E van de Wal, Merel J W Adjobo-Hermans, Jaap Keijer, Tom J J Schirris, Judith R Homberg, Mariusz R Wieckowski, Sander Grefte, Evert M van Schothorst, Clara van Karnebeek, Albert Quintana and 1 more

Open access · bronzeAbstract readReview
In one paragraph

Review in Brain : a journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
4.9field-weighted citation impact, top 3% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

60 citing papers in PubMed, 86 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. CoQExperimental & molecular medicine · 2026
    Review
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  6. Article
  7. Article
  8. Article
  9. Targetable Effects of the Anesthetic, Ubiquinone-5, on Murine Cardiac Rhythm.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  10. Article
  11. Article
  12. Article
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  14. Gene therapy and mRNA drugs approach for mitochondrial OXPHOS deficiencies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  15. Article
  16. Review
  17. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 3 countries.

Melissa A E van de WalDepartment of Pediatrics, Amalia Children's Hospital, RIMLS, RCMM, Radboudumc, Nijmegen, The Netherlands.
Merel J W Adjobo-HermansDepartment of Biochemistry (286), RIMLS, RCMM, Radboudumc, Nijmegen, The Netherlands.ORCID 0000-0002-5947-2876
Jaap KeijerHuman and Animal Physiology, Wageningen University, Wageningen, The Netherlands.ORCID 0000-0002-9720-7491
Tom J J SchirrisDepartment of Pharmacology and Toxicology, RIMLS, RCMM, Radboudumc, Nijmegen, The Netherlands.ORCID 0000-0002-7621-1010
Judith R HombergDepartment of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboudumc, Nijmegen, The Netherlands.
Mariusz R WieckowskiLaboratory of Mitochondrial Biology and Metabolism, Nencki Institute of Experimental Biology, Warsaw, Poland.ORCID 0000-0003-0789-4521
Sander GrefteHuman and Animal Physiology, Wageningen University, Wageningen, The Netherlands.ORCID 0000-0002-8502-6298
Evert M van SchothorstHuman and Animal Physiology, Wageningen University, Wageningen, The Netherlands.ORCID 0000-0002-3036-5903
Clara van KarnebeekDepartment of Pediatrics, Amalia Children's Hospital, RIMLS, RCMM, Radboudumc, Nijmegen, The Netherlands.ORCID 0000-0002-2648-8337
Albert QuintanaMitochondrial Neuropathology Laboratory, Institut de Neurociències and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Spain.ORCID 0000-0003-1674-7160
Werner J H KoopmanDepartment of Pediatrics, Amalia Children's Hospital, RIMLS, RCMM, Radboudumc, Nijmegen, The Netherlands.ORCID 0000-0002-3364-0069
Radboud University Nijmegen · NLWageningen University & Research · NLInstytut Biologii Doświadczalnej im. Marcelego Nenckiego · PLUniversitat Autònoma de Barcelona · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mitochondria are small cellular constituents that generate cellular energy (ATP) by oxidative phosphorylation (OXPHOS). Dysfunction of these organelles is linked to a heterogeneous group of multisystemic disorders, including diabetes, cancer, ageing-related pathologies and rare mitochondrial diseases. With respect to the latter, mutations in subunit-encoding genes and assembly factors of the first OXPHOS complex (complex I) induce isolated complex I deficiency and Leigh syndrome. This syndrome is an early-onset, often fatal, encephalopathy with a variable clinical presentation and poor prognosis due to the lack of effective intervention strategies. Mutations in the nuclear DNA-encoded NDUFS4 gene, encoding the NADH:ubiquinone oxidoreductase subunit S4 (NDUFS4) of complex I, induce 'mitochondrial complex I deficiency, nuclear type 1' (MC1DN1) and Leigh syndrome in paediatric patients. A variety of (tissue-specific) Ndufs4 knockout mouse models were developed to study the Leigh syndrome pathomechanism and intervention testing. Here, we review and discuss the role of complex I and NDUFS4 mutations in human mitochondrial disease, and review how the analysis of Ndufs4 knockout mouse models has generated new insights into the MC1ND1/Leigh syndrome pathomechanism and its therapeutic targeting.

Indexed as

Electron Transport Complex ILeigh DiseaseMitochondrial DiseasesAnimalsHumansMiceMice, KnockoutOxidative PhosphorylationElectron Transport Complex INDUFS4 protein, humanNdufs4 protein, mouseinterventionLeigh syndromemouse modelpathomechanism

Identifiers

PMID34849584
PMCPMC8967107
OpenAlexW3215232751

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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 Socratic graph.