Idebenone attenuates ferroptosis by inhibiting excessive autophagy via the ROS-AMPK-mTOR pathway to preserve cardiac function after myocardial infarction

• DOI: 10.1016/j.ejphar.2023.175569
• Publication Date: 2023-02-03T07:40:09Z
• Authors: Demin Li; Ge Zhang; Zeyu Wang; Jiacheng Guo; Yu Liu; Yongzheng Lu; Zhen Qin; Yanyan Xu; Chang Cao; Bo Wang; Qianqian Guo; Yunzhe Wang; Guozhen Liu; Xiaolin Cui; Jinying Zhang; Junnan Tang
• Keywords: Idebenone; Coenzyme Q10; Mitochondrial ROS; Cardioprotection

Cardiovascular diseases (CVDs) are the leading causes of mortality worldwide. As a type CVDs, myocardial infarction (MI) induces ischemia hypoxia, which leads to excessive reactive oxygen species (ROS), resulting in multiple cell deaths and contributing subsequent development heart failure or premature death. Recent evidence indicates that ROS-induced lipid peroxidation promotes autophagy ferroptosis, loss healthy myocardium dysfunction cardiac tissue. Theoretically, function would be preserved after MI by inhibiting ferroptosis. an analog coenzyme Q10 (CoQ10) clinically approved drug, idebenone used inhibit ferroptosis preserve due its capacity improve mitochondrial physiology with antioxidant anti-inflammatory properties. Here, we confirmed addition inhibited H2O2-induced RSL3-induced Furthermore, ROS-AMPK-mTOR pathway axis was identified as signaling stimulated prevent consequent In animal model, demonstrated cardioprotective role regulating ROS-dependent paves way for future clinical translation management.