2026-05-20T03:47:28Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/188572024-02-27T15:24:39Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927col_20.500.12105_16970col_20.500.12105_16975
Repisalud
author
González-Recio, Irene
author
Simón, Jorge
author
Goikoetxea-Usandizaga, Naroa
author
Serrano-Maciá, Marina
author
Mercado-Gómez, Maria
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Rodríguez-Agudo, Rubén
author
Lachiondo-Ortega, Sofía
author
Gil-Pitarch, Clàudia
author
Fernández-Rodríguez, Carmen
author
Castellana, Donatello
author
Latasa, Maria U
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Abecia, Leticia
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Anguita, Juan
author
Delgado, Teresa C
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Iruzubieta, Paula
author
Crespo, Javier
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Hardy, Serge
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Petrov, Petar D
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Jover, Ramiro
author
Avila, Matías A
author
Martín, César
author
Schaeper, Ute
author
Tremblay, Michel L
author
Dear, James W
author
Masson, Steven
author
McCain, Misti Vanette
author
Reeves, Helen L
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Andrade, Raul J
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Lucena, M Isabel
author
Buccella, Daniela
author
Martínez-Cruz, Luis Alfonso
author
Martínez-Chantar, Maria L
2024-02-27T15:24:39Z
2024-02-27T15:24:39Z
2022-11-25
10.1038/s41467-022-34262-0
2041-1723
Nature communications
http://hdl.handle.net/10668/19549
36433951
http://hdl.handle.net/20.500.12105/18857
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.
eng
Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage.
research article