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, Maria U. Latasa, Leticia Abecia, Juan Anguita, Teresa C. Delgado, Paula Iruzubieta, Javier Crespo, Serge Hardy, Petar D. Petrov, Ramiro Jover, Matías A. Avila, César Martín, Ute Schaeper, Michel L. Tremblay, James W. Dear, Steven Masson, Misti Vanette McCain, Helen L. Reeves, Raul J. Andrade, M. Isabel Lucena, Daniela Buccella (), Luis Alfonso Martínez-Cruz () and Maria L Martínez-Chantar ()
Additional contact information
Irene González-Recio: Bizkaia Technology Park
Jorge Simón: Bizkaia Technology Park
Naroa Goikoetxea-Usandizaga: Bizkaia Technology Park
Marina Serrano-Maciá: Bizkaia Technology Park
Maria Mercado-Gómez: Bizkaia Technology Park
Rubén Rodríguez-Agudo: Bizkaia Technology Park
Sofía Lachiondo-Ortega: Bizkaia Technology Park
Clàudia Gil-Pitarch: Bizkaia Technology Park
Carmen Fernández-Rodríguez: Bizkaia Technology Park
Donatello Castellana: Bizkaia Technology Park
Maria U. Latasa: Universidad de Navarra
Leticia Abecia: Basque Research and Technology Alliance (BRTA)
Juan Anguita: Basque Research and Technology Alliance (BRTA)
Teresa C. Delgado: Bizkaia Technology Park
Paula Iruzubieta: Marqués de Valdecilla University Hospital, Clinical and Translational Digestive Research Group, IDIVAL
Javier Crespo: Marqués de Valdecilla University Hospital, Clinical and Translational Digestive Research Group, IDIVAL
Serge Hardy: McGill University
Petar D. Petrov: Carlos III National Health Institute
Ramiro Jover: Carlos III National Health Institute
Matías A. Avila: Carlos III National Health Institute
César Martín: University of the Basque Country (UPV/EHU)
Ute Schaeper: Silence Therapeutics GmbH, Berlin
Michel L. Tremblay: McGill University
James W. Dear: University of Edinburgh
Steven Masson: Newcastle-upon-Tyne Hospitals NHS Foundation Trust
Misti Vanette McCain: Newcastle-upon-Tyne Hospitals NHS Foundation Trust
Helen L. Reeves: Newcastle-upon-Tyne Hospitals NHS Foundation Trust
Raul J. Andrade: Carlos III National Health Institute
M. Isabel Lucena: Carlos III National Health Institute
Daniela Buccella: New York University
Luis Alfonso Martínez-Cruz: Bizkaia Technology Park
Maria L Martínez-Chantar: Bizkaia Technology Park

Nature Communications, 2022, vol. 13, issue 1, 1-21

Abstract: 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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-34262-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34262-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-34262-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().