溶酶体：AMPK信号调控的新枢纽——机制、功能与疾病关联

Lysosome: A New Hub for AMPK Signaling Regulation—Mechanisms, Functions, and Disease Connections

摘要: 溶酶体是真核细胞内负责降解与代谢调控的核心细胞器。近年研究发现，经典的能量感受器——AMP活化蛋白激酶(AMPK)可定位于溶酶体，并在此整合多种信号，从而超越了其传统的能量感知功能。本文聚焦于溶酶体AMPK通路的核心作用，该通路通过葡萄糖感知、膜损伤感应与钙信号等多条途径被激活，并与溶酶体mTOR通路相互协同，构成一个动态、精密的代谢调控网络，使AMPK升级为全局性的“代谢状态整合器”。这一枢纽地位在多种生理与病理过程中至关重要：它不仅是二甲双胍、热量限制等干预措施发挥健康益处的共同节点，也在代谢性疾病、衰老、癌症及神经退行性疾病中发挥核心调控作用。本文旨在系统总结该通路的分子机制、生理病理功能及转化潜力，以期为理解细胞代谢调控和开发疾病治疗新策略提供理论基础。

Abstract: Lysosomes are core organelles in eukaryotic cells responsible for degradation and metabolic regulation. Recent studies have revealed that the classic energy sensor—AMP-activated protein kinase (AMPK)—can localize to lysosomes, where it integrates multiple signals, thereby extending its function beyond traditional energy sensing. This review focuses on the central role of the lysosomal AMPK pathway. Activated via multiple routes, including glucose sensing, membrane damage sensing, and calcium signaling, and operating in coordination with the lysosomal mTOR pathway, it forms a dynamic and precise regulatory network that elevates AMPK to the status of a global “integrator of metabolic status”. This pivotal role is crucial in various physiological and pathological processes: it serves as a common node through which interventions such as metformin and caloric restriction exert their health benefits, and it plays a core regulatory role in metabolic diseases, aging, cancer, and neurodegenerative disorders. This article aims to systematically summarize the molecular mechanisms, pathophysiological functions, and translational potential of this pathway, in order to provide a theoretical foundation for understanding cellular metabolic regulation and developing novel therapeutic strategies.