Bao Yongfen, Ma Yaoyao, Huang Wentao, Bai Yujie, Gao Siying, Xiu Luyao, Xie Yuyang, Wan Xinrong, Shan Shigang, Chen Chao, Qu Lihua
Hubei Key Laboratory of Diabetes and Angiopathy, School of Pharmacy, Hubei University of Science and Technology, Xianning 437000, China; School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning 437000, China.
Department of Physiology, Hunan Normal University School of Medicine, Changsha 410013, China.
Int J Biol Macromol. 2025 Feb;291:139057. doi: 10.1016/j.ijbiomac.2024.139057. Epub 2024 Dec 20.
Autophagy is a highly conserved catabolic pathway that is precisely regulated and plays a significant role in maintaining cellular metabolic balance and intracellular homeostasis. Abnormal autophagy is directly linked to the development of various diseases, particularly immune disorders, neurodegenerative conditions, and tumors. The precise regulation of proteins is crucial for proper cellular function, and post-translational modifications (PTMs) are key epigenetic mechanisms in the regulation of numerous biological processes. Multiple proteins undergo PTMs that influence autophagy regulation. Methylation modifications on non-histone lysine and arginine residues have been identified as common PTMs critical to various life processes. This paper focused on the regulatory effects of non-histone methylation modifications on autophagy, summarizing related research on signaling pathways involved in autophagy-related non-histone methylation, and discussing current challenges and clinical significance. Our review concludes that non-histone methylation plays a pivotal role in the regulation of autophagy and its associated signaling pathways. Targeting non-histone methylation offers a promising strategy for therapeutic interventions in diseases related to autophagy dysfunction, such as cancer and neurodegenerative disorders. These findings provide a theoretical basis for the development of non-histone-methylation-targeted drugs for clinical use.
自噬是一种高度保守的分解代谢途径，受到精确调控，在维持细胞代谢平衡和细胞内稳态方面发挥着重要作用。自噬异常与多种疾病的发生直接相关，尤其是免疫紊乱、神经退行性疾病和肿瘤。蛋白质的精确调控对于细胞的正常功能至关重要，而翻译后修饰（PTM）是调节众多生物学过程的关键表观遗传机制。多种蛋白质会经历影响自噬调控的PTM。非组蛋白赖氨酸和精氨酸残基上的甲基化修饰已被确定为对各种生命过程至关重要的常见PTM。本文重点关注非组蛋白甲基化修饰对自噬的调控作用，总结自噬相关非组蛋白甲基化所涉及信号通路的相关研究，并探讨当前面临的挑战和临床意义。我们的综述得出结论，非组蛋白甲基化在自噬及其相关信号通路的调控中起关键作用。针对非组蛋白甲基化提供了一种有前景的策略，用于对与自噬功能障碍相关的疾病（如癌症和神经退行性疾病）进行治疗干预。这些发现为开发用于临床的非组蛋白甲基化靶向药物提供了理论基础。
