Evidence map›Paper›PMID 36433951›Full record

ArticleNature communications2022

Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage.

Irene González-Recio, Jorge Simón, Naroa Goikoetxea-Usandizaga, Marina Serrano-Maciá, Maria Mercado-Gómez, Rubén Rodríguez-Agudo, Sofía Lachiondo-Ortega, Clàudia Gil-Pitarch, Carmen Fernández-Rodríguez, Donatello Castellana and 22 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
5.8field-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

20 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
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  7. Review
  8. Metal Ion Signaling in Biomedicine.Chemical reviews · 2025
    Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. NLRP3 Inflammasome in Acute and Chronic Liver Diseases.International journal of molecular sciences · 2024
    Review
  16. Dimerization of the CNNM extracellular domain.Protein science : a publication of the Protein Society · 2024
    Article
  17. Article
  18. Magnesium and Liver Metabolism Through the Lifespan.Advances in nutrition (Bethesda, Md.) · 2023
    Review
  19. Article
  20. Review
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

32 authors at 13 institutions in 5 countries.

Irene González-RecioLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160, Derio, Spain.
Jorge SimónLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160, Derio, Spain.
Naroa Goikoetxea-UsandizagaLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160, Derio, Spain.ORCID 0000-0003-4569-028X
Marina Serrano-MaciáLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160, Derio, Spain.ORCID 0000-0003-4183-6384
Maria Mercado-GómezLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160, Derio, Spain.
Rubén Rodríguez-AgudoLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160, Derio, Spain.ORCID 0000-0001-5731-5052
Sofía Lachiondo-OrtegaLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160, Derio, Spain.ORCID 0000-0003-1856-3664
Clàudia Gil-PitarchLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160, Derio, Spain.ORCID 0000-0003-2220-0612
Carmen Fernández-RodríguezLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160, Derio, Spain.
Donatello CastellanaResearch & Development, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160, Derio, Spain.
Maria U LatasaHepatology Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, 31008, Pamplona, Spain.ORCID 0000-0002-0878-1337
Leticia AbeciaInflammation and Macrophage Plasticity Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), 48160, Derio, Bizkaia, Spain.ORCID 0000-0003-4097-8903
Juan AnguitaInflammation and Macrophage Plasticity Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), 48160, Derio, Bizkaia, Spain.ORCID 0000-0003-2061-7182
Teresa C DelgadoLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160, Derio, Spain.ORCID 0000-0001-9204-581X
Paula IruzubietaGastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, Clinical and Translational Digestive Research Group, IDIVAL, Santander, Spain.
Javier CrespoGastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, Clinical and Translational Digestive Research Group, IDIVAL, Santander, Spain.ORCID 0000-0001-8248-0172
Serge HardyDepartment of Biochemistry, McGill University, H3G 1Y6, Montréal, QC, Canada.
Petar D PetrovCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, Spain.ORCID 0000-0001-9697-4317
Ramiro JoverCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, Spain.ORCID 0000-0002-4914-5804
Matías A AvilaCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, Spain.ORCID 0000-0001-6570-3557
César MartínBiofisika Institute (UPV/EHU, CSIC) and Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), 48940, Leioa, Spain.
Ute SchaeperSilence Therapeutics GmbH, Berlin, Robert Rössle Strasse 10, 13125, Berlin, Germany.ORCID 0000-0003-2556-8391
Michel L TremblayDepartment of Biochemistry, McGill University, H3G 1Y6, Montréal, QC, Canada.ORCID 0000-0002-0281-541X
James W DearPharmacology, Toxicology and Therapeutics, Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.ORCID 0000-0002-8630-8625
Steven MassonThe Liver Unit, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE7 7DN, UK.
Misti Vanette McCainThe Liver Unit, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE7 7DN, UK.ORCID 0000-0002-1967-0421
Helen L ReevesThe Liver Unit, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE7 7DN, UK.ORCID 0000-0003-0359-9795
Raul J AndradeCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, Spain.ORCID 0000-0002-1565-0757
M Isabel LucenaCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, Spain.ORCID 0000-0001-9586-4896
Daniela BuccellaDepartment of Chemistry, New York University, New York, NY, 10003, USA. dbuccella@nyu.edu.ORCID 0000-0002-2266-9026
Luis Alfonso Martínez-CruzLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160, Derio, Spain. amartinez@cicbiogune.es.ORCID 0000-0002-5856-9377
Maria L Martínez-ChantarLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160, Derio, Spain. mlmartinez@cicbiogune.es.ORCID 0000-0002-6446-9911
CIC bioGUNE · ESNewcastle upon Tyne Hospitals NHS Foundation Trust · GBCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas · ESMarqués de Valdecilla University Hospital · ESMcGill University Health Centre · CAUniversitat de València · ESUniversity of the Basque Country · ESIkerbasque · ESNew York University · USSilence Therapeutics (Germany) · DESpanish Clinical Research Network · ESUniversidad de Navarra · ESUniversity of Edinburgh · GB

Funding

Molecular Probes Shed Light on Magnesium HomeostasisR01CA217817 · NCI · NEW YORK UNIVERSITY · PI BUCCELLA, DANIELA · 2017 to 2021
$1.7M
Cancer Research UK 26813NCI NIH HHS R01 CA217817
6 · The paper itself

Abstract

Acetaminophen overdose is one of the leading causes of acute liver failure and liver transplantation in the Western world. Magnesium is essential in several cellular processess. The Cyclin M family is involved in magnesium transport across cell membranes. Herein, we identify that among all magnesium transporters, only Cyclin M4 expression is upregulated in the liver of patients with acetaminophen overdose, with disturbances in magnesium serum levels. In the liver, acetaminophen interferes with the mitochondrial magnesium reservoir via Cyclin M4, affecting ATP production and reactive oxygen species generation, further boosting endoplasmic reticulum stress. Importantly, Cyclin M4 mutant T495I, which impairs magnesium flux, shows no effect. Finally, an accumulation of Cyclin M4 in endoplasmic reticulum is shown under hepatoxicity. Based on our studies in mice, silencing hepatic Cyclin M4 within the window of 6 to 24 h following acetaminophen overdose ingestion may represent a therapeutic target for acetaminophen overdose induced liver injury.

Indexed as

AcetaminophenCation Transport ProteinsChemical and Drug Induced Liver InjuryLiver DiseasesMagnesiumAnimalsCyclinsMiceAcetaminophenCation Transport ProteinsCnnm4 protein, mouseCyclinsMagnesium

Identifiers

PMID36433951
PMCPMC9700862
OpenAlexW4309941554

What Socratic holds

Textmetadata
LicenceCC BY
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.