Core Viewpoint - The article discusses the discovery of a novel membraneless organelle called Lipid-induced granule (LIG) in hepatocytes, which is induced by lipid accumulation and has implications for understanding liver fibrosis and potential intervention targets for fatty liver disease [3][9]. Group 1: Discovery and Characteristics of LIG - A new type of membraneless organelle, named Lipid-induced granule (LIG), has been identified in hepatocytes, revealing its characteristics, formation, and function [3]. - LIG is formed through the liquid-liquid phase separation (LLPS) of the DDX49 protein, which is induced by lipid metabolites, particularly arachidonic acid [10]. Group 2: Mechanism of Action - LIG plays a role in inhibiting the progression of metabolic dysfunction-associated fatty liver disease (MASLD) by feedback inhibition of the pro-fibrotic liver factor TIMP2 [10]. - The mechanism involves the recruitment of m5C-modified Timp2 mRNA and its reader YBX1 to LIG, which suppresses the translation of Timp2 mRNA, thereby inhibiting liver fibrosis [7][10]. Group 3: Clinical Relevance - The presence of LIG has been identified in human MASLD livers, and its abundance is negatively correlated with the progression of fibrosis [8]. - The global prevalence of MASLD is estimated to be 30% among adults, with its severe form, MASH, leading to liver fibrosis and significant health risks [6].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 能量感应器 AMPK 在应激条件下促进肿瘤细胞的存活，然而，如何阻止 AMPK 的激活以抑制肿瘤进展，目前仍不清楚。 在这项最新研究中，研究团队发现，代谢物 α-酮戊二酸 （α-KG） 通过 TET-YBX1 信号轴调控 AMPK 的翻译和 AMPK 蛋白的合成，这一机制可用于增强人类 癌细胞对能量应激的敏感性。 代谢失调 是 癌症 的一个显著特征。癌细胞会经历代谢重塑，以维持生物合成，从而在氧气和营养物质有限的恶劣肿瘤微环境中生存下来，并逃避免疫监视或药 物治疗。 在癌症代谢适应应激的过程中，一种不可或缺的调控因子是 AMPK ，它也被称为 能量感应器 。AMPK 的激活会抑制脂质和蛋白质合成，刺激葡萄糖摄取、脂肪 酸氧化以及线粒体和溶酶体的生成，共同维持能量和氧化还原平衡。AMPK 的失活则会抑制体内肿瘤的进展。因此，阻断 AMPK 激活以使癌细胞失去能量感知， 可能在能量应激条件下从功能上抑制肿瘤生长，然而，目前尚缺乏可行的治疗策略来实现这一目标。 2025 年 8 月 22 日，复旦大学代谢与整合生物学研究院 李福明 团队联合 中国科学院分子细胞卓越科学创新中心 ...