RT Journal Article
T1 The mitochondrial negative regulator MCJ is a therapeutic target for acetaminophen-induced liver injury.
A1 Barbier-Torres, Lucía
A1 Iruzubieta, Paula
A1 Fernández-Ramos, David
A1 Delgado, Teresa C
A1 Taibo, Daniel
A1 Guitiérrez-de-Juan, Virginia
A1 Varela-Rey, Marta
A1 Azkargorta, Mikel
A1 Navasa, Nicolas
A1 Fernández-Tussy, Pablo
A1 Zubiete-Franco, Imanol
A1 Simon, Jorge
A1 Lopitz-Otsoa, Fernando
A1 Lachiondo-Ortega, Sofia
A1 Crespo, Javier
A1 Masson, Steven
A1 McCain, Misti Vanette
A1 Villa, Erica
A1 Reeves, Helen
A1 Elortza, Felix
A1 Lucena, Maria Isabel
A1 Hernández-Alvarez, Maria Isabel
A1 Zorzano, Antonio
A1 Andrade, Raúl J
A1 Lu, Shelly C
A1 Mato, José M
A1 Anguita, Juan
A1 Rincón, Mercedes
A1 Martínez-Chantar, María Luz
AB Acetaminophen (APAP) is the active component of many medications used to treat pain and fever worldwide. Its overuse provokes liver injury and it is the second most common cause of liver failure. Mitochondrial dysfunction contributes to APAP-induced liver injury but the mechanism by which APAP causes hepatocyte toxicity is not completely understood. Therefore, we lack efficient therapeutic strategies to treat this pathology. Here we show that APAP interferes with the formation of mitochondrial respiratory supercomplexes via the mitochondrial negative regulator MCJ, and leads to decreased production of ATP and increased generation of ROS. In vivo treatment with an inhibitor of MCJ expression protects liver from acetaminophen-induced liver injury at a time when N-acetylcysteine, the standard therapy, has no efficacy. We also show elevated levels of MCJ in the liver of patients with acetaminophen overdose. We suggest that MCJ may represent a therapeutic target to prevent and rescue liver injury caused by acetaminophen.
YR 2017
FD 2017-12-12
LK http://hdl.handle.net/10668/11900
UL http://hdl.handle.net/10668/11900
LA en
DS RISalud
RD Apr 11, 2025