具体而言，细胞在营养匮乏时，名为"乙酰辅酶A"的"神秘信使"出动，它会绕过科学家们熟知的AMPK 和mTOR这两条营养感知的"经典主干道"，独辟蹊径地将"饥饿"信号直抵细胞能量工厂——线粒体，指 挥"哨兵"NLRX1作出响应。这项发现不仅解释了适度饥饿如何触发身体的积极反应，还将为未来对抗 代谢性疾病、癌症乃至延缓衰老开辟了一条充满想象的全新研究道路。 近年来，"轻断食"之风流行，人们通过控制进食时间让身体保持适度饥饿，以此调动脂肪、稳定血糖， 清除体内的老废代谢物。这背后的原因是什么？11月13日，复旦大学雷群英团队在国际学术期刊《自 然》(Nature)在线发表研究论文，提供了解释。 这项历经近10年探索的研究，首次揭示了乙酰辅酶A作为"代谢信使"的非经典功能，突破传统认知，发 现其可直接调控线粒体自噬，为克服胰腺癌KRAS抑制剂耐药提供了全新治疗靶点，在代谢生物学与肿 瘤学交叉领域取得突破性进展。 复旦大学基础医学院/肿瘤研究所教授雷群英回忆，2016年年底她就与团队成员立下"flag"：要做不依赖 经典代谢感知通路的创新研究。团队模拟人体"温和饥饿"环境，用接近人体过夜饥饿的营养成分配制培 养基。实验 ...

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]