Details

Autor(en) / Beteiligte

• Barbier-Torres, Lucía
• Iruzubieta, Paula
• Fernández-Ramos, David
• Delgado, Teresa C.
• Taibo, Daniel
• Guitiérrez-de-Juan, Virginia
• Varela-Rey, Marta
• Azkargorta, Mikel
• Navasa, Nicolas
• Fernández-Tussy, Pablo
• Zubiete-Franco, Imanol
• Simon, Jorge
• Lopitz-Otsoa, Fernando
• Lachiondo-Ortega, Sofia
• Crespo, Javier
• Masson, Steven
• McCain, Misti Vanette
• Villa, Erica
• Reeves, Helen
• Elortza, Felix
• Lucena, Maria Isabel
• Hernández-Alvarez, Maria Isabel
• Zorzano, Antonio
• Andrade, Raúl J.
• Lu, Shelly C.
• Mato, José M.
• Anguita, Juan
• Rincón, Mercedes
• Martínez-Chantar, María Luz

Titel

The mitochondrial negative regulator MCJ is a therapeutic target for acetaminophen-induced liver injury

Ist Teil von

• Nature communications, 2017-12, Vol.8 (1), p.2068-11, Article 2068

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. Acetaminophen-induced liver injury is one of the most common causes of liver failure and has to be treated within hours of the overdose. Here Barbier-Torres et al. show that targeting MCJ, a mitochondrial negative regulator, even 24 h after the overdose protects liver from acetaminophen-induced damage.