Department of Molecular, Cellular and Developmental Biology, Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
FEBS Lett. 2024 Jan;598(1):32-47. doi: 10.1002/1873-3468.14741. Epub 2023 Oct 9.
Macroautophagy/autophagy is a highly conserved catabolic process vital for cellular stress responses and maintaining equilibrium within the cell. Malfunctioning autophagy has been implicated in the pathogenesis of various diseases, including certain neurodegenerative disorders, diabetes, metabolic diseases, and cancer. Cells face diverse metabolic challenges, such as limitations in nitrogen, carbon, and minerals such as phosphate and iron, necessitating the integration of complex metabolic information. Cells utilize a signal transduction network of sensors, transducers, and effectors to coordinate the execution of the autophagic response, concomitant with the severity of the nutrient-starvation condition. This review presents the current mechanistic understanding of how cells regulate the initiation of autophagy through various nutrient-dependent signaling pathways. Emphasizing findings from studies in yeast, we explore the emerging principles that underlie the nutrient-dependent regulation of autophagy, significantly shaping stress-induced autophagy responses under various metabolic stress conditions.
自噬是一种高度保守的分解代谢过程,对细胞应激反应和维持细胞内平衡至关重要。自噬功能障碍与多种疾病的发病机制有关,包括某些神经退行性疾病、糖尿病、代谢疾病和癌症。细胞面临着多种代谢挑战,如氮、碳和磷、铁等矿物质的限制,因此需要整合复杂的代谢信息。细胞利用传感器、转导器和效应器的信号转导网络来协调自噬反应的执行,同时伴随着营养饥饿程度的加重。本综述介绍了细胞如何通过各种营养依赖的信号通路来调节自噬起始的机制理解。强调来自酵母研究的发现,我们探讨了营养依赖的自噬调节的新兴原则,这些原则显著影响了各种代谢应激条件下应激诱导的自噬反应。