自噬是一种溶酶体介导的自我降解过程，对于细胞质量控制至关重要。它还为营养或能量缺乏期间的能量代谢提供大分子构建块和底物，这是自噬诱导的主要刺激物。然而，与大多数生物过程一样，自噬本身需要 ATP，并且其启动和执行存在能量阈值。我们在此首次全面回顾自噬研究中经常被忽视的这一方面。 ATP 缺乏在体外和体内抑制自噬的研究根据所涉及的能量途径（氧化磷酸化或糖酵解）进行分类。通过查明关键的 ATP 消耗自噬事件，包括自噬相关分子的转录/翻译/相互作用、自噬体形成/延伸、自噬体与溶酶体融合以及溶酶体酸化，提供了机制见解。讨论了自噬反应的能量依赖性微调对于保持细胞稳态的重要性，以及对癌症、自身免疫、代谢紊乱和神经退行性疾病治疗的潜在影响。© 2024 Wiley periodicals LLC。

Autophagy is a lysosome-mediated self-degradation process of central importance for cellular quality control. It also provides macromolecule building blocks and substrates for energy metabolism during nutrient or energy deficiency, which are the main stimuli for autophagy induction. However, like most biological processes, autophagy itself requires ATP, and there is an energy threshold for its initiation and execution. We here present the first comprehensive review of this often-overlooked aspect of autophagy research. The studies in which ATP deficiency suppressed autophagy in vitro and in vivo were classified according to the energy pathway involved (oxidative phosphorylation or glycolysis). A mechanistic insight was provided by pinpointing the critical ATP-consuming autophagic events, including transcription/translation/interaction of autophagy-related molecules, autophagosome formation/elongation, autophagosome fusion with the lysosome, and lysosome acidification. The significance of energy-dependent fine-tuning of autophagic response for preserving the cell homeostasis, and potential implications for the therapy of cancer, autoimmunity, metabolic disorders, and neurodegeneration are discussed.© 2024 Wiley Periodicals LLC.