复旦大学最新Nature论文：禁食是把双刃剑，激活线粒体自噬，促进癌症耐药

Core Insights - The research published by Fudan University reveals a novel signaling function of Acetyl-Coenzyme A (AcCoA) in regulating mitophagy through the receptor NLRX1, independent of classical pathways like AMPK and mTOR [3][14][16] - This discovery provides new potential targets and strategies for overcoming resistance to KRAS inhibitors in cancer treatment [3][14][16] Group 1: Mechanism of AcCoA in Mitophagy - AcCoA levels decrease during nutrient deprivation, such as short-term fasting, leading to the activation of mitophagy [5][6] - NLRX1 is identified as a key mediator that directly binds to AcCoA, regulating its signaling role in mitophagy [8][11] Group 2: Experimental Validation - In animal models, fasting resulted in a significant decrease in AcCoA levels in tissues, correlating with increased mitophagy [11] - Supplementing with acetate or knocking out NLRX1 gene can block the fasting-induced mitophagy, indicating the critical role of AcCoA and NLRX1 in this process [11][12] Group 3: Implications for Cancer Treatment - The study indicates that KRAS inhibitors downregulate ACLY expression, reducing AcCoA levels and triggering NLRX1-dependent mitophagy, which may contribute to cancer cell resistance [14] - Short-term fasting may have dual effects in cancer treatment, potentially enhancing immune response while also promoting resistance through mitophagy [14][16] Group 4: Future Directions - Targeting the AcCoA-NLRX1 signaling axis may enhance cancer treatment efficacy and could have implications in various metabolic and neurodegenerative diseases [16]