RT Journal Article
T1 Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage.
A1 González-Recio, Irene
A1 Simón, Jorge
A1 Goikoetxea-Usandizaga, Naroa
A1 Serrano-Maciá, Marina
A1 Mercado-Gómez, Maria
A1 Rodríguez-Agudo, Rubén
A1 Lachiondo-Ortega, Sofía
A1 Gil-Pitarch, Clàudia
A1 Fernández-Rodríguez, Carmen
A1 Castellana, Donatello
A1 Latasa, Maria U
A1 Abecia, Leticia
A1 Anguita, Juan
A1 Delgado, Teresa C
A1 Iruzubieta, Paula
A1 Crespo, Javier
A1 Hardy, Serge
A1 Petrov, Petar D
A1 Jover, Ramiro
A1 Avila, Matías A
A1 Martín, César
A1 Schaeper, Ute
A1 Tremblay, Michel L
A1 Dear, James W
A1 Masson, Steven
A1 McCain, Misti Vanette
A1 Reeves, Helen L
A1 Andrade, Raul J
A1 Lucena, M Isabel
A1 Buccella, Daniela
A1 Martínez-Cruz, Luis Alfonso
A1 Martínez-Chantar, Maria L
AB 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.
YR 2022
FD 2022-11-25
LK http://hdl.handle.net/10668/19549
UL http://hdl.handle.net/10668/19549
LA en
DS RISalud
RD Apr 7, 2025