Zhao Yuqian, Qu Tiange, Wang Peiqi, Li Xinyi, Qiang Jiayu, Xia Zhaokun, Duan Hangwu, Huang Jian, Zhu Lingjuan
Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China.
School of Basic Medicine Science, Beijing University of Chinese Medicine, Beijing, 100029, China.
Apoptosis. 2016 May;21(5):517-31. doi: 10.1007/s10495-016-1236-3.
Macroautophagy (Autophagy), an evolutionarily conserved cellular self-digesting process implicated in various physiological and pathological processes, is activated by different stimuli including oxidative stress. Reactive oxygen species (ROS) are involved in autophagy modulation through multiple signaling pathways and transcription regulators. Accumulating data support both a positive and negative role of ROS-modulated autophagy in cancer. As a tumor suppressive mechanism, autophagy induces autophagic cell death and maintains genome stability. Conversely, autophagy may promote cancer development by limiting metabolic stress and supplying high-energetic nutrients. Mitochondrial ROS (mitoROS), the main source of endogenous ROS, serve as essential signal transducers that mediate autophagy, while autophagy can also regulate mitochondrial ROS generation in turn. Here, we untangle the knot between mitochondrial ROS and autophagy, which may be of great significance to solve the conundrum of the inter-conversion between cytoprotective and cytotoxic roles of autophagy; thus providing new insights for current cancer therapies. Whilst, we focus on anti-tumor agents that target mitoROS-regulated autophagy, in the hope of fueling the exploration of more potential novel anti-cancer drugs in the future.
巨自噬（自噬）是一种在进化上保守的细胞自我消化过程，涉及多种生理和病理过程，可被包括氧化应激在内的不同刺激激活。活性氧（ROS）通过多种信号通路和转录调节因子参与自噬调节。越来越多的数据支持ROS调节的自噬在癌症中既具有正向作用也具有负向作用。作为一种肿瘤抑制机制，自噬诱导自噬性细胞死亡并维持基因组稳定性。相反，自噬可能通过限制代谢应激和提供高能营养物质来促进癌症发展。线粒体ROS（mitoROS）是内源性ROS的主要来源，作为介导自噬的重要信号转导分子，而自噬反过来也可以调节线粒体ROS的产生。在这里，我们解开线粒体ROS与自噬之间的纠结，这对于解决自噬在细胞保护和细胞毒性作用之间相互转换的难题可能具有重要意义；从而为当前的癌症治疗提供新的见解。同时，我们专注于靶向mitoROS调节的自噬的抗肿瘤药物，希望在未来推动对更多潜在新型抗癌药物的探索。
