Ataxia-telangiectasia突变 (ATM)是DNA损伤反应 (DDR)的主要激酶，它磷酸化大量底物，在DNA双链断裂后激活信号通路。ATM抑制剂已被评估为抗癌药物，用于增强基于DNA损伤的癌症治疗的细胞毒性。ATM还参与自噬，这是一种维持细胞稳态的保守细胞过程，通过降解不必要的蛋白质和功能失调的细胞器。本研究报告了ATM抑制剂(KU-55933和KU-60019)诱导自噬体和p62积累，抑制自溶体形成。在诱导自噬条件下，ATM抑制剂会导致过多的自噬体积累和细胞死亡。这种ATM在自噬中的新功能也被观察到在许多细胞系中。使用siRNA抑制ATM表达，在自噬诱导条件下抑制了自溶体形成步骤的自噬通路，并诱导了细胞死亡。综上所述，我们的结果表明，ATM参与自溶体形成，ATM抑制剂在癌症治疗中的使用可能会扩展。

Ataxia-telangiectasia mutated (ATM), a master kinase of the DNA damage response (DDR), phosphorylates a multitude of substrates to activate signaling pathways after DNA double-strand breaks (DSBs). ATM inhibitors have been evaluated as anticancer drugs to potentiate the cytotoxicity of DNA damage-based cancer therapy. ATM is also involved in autophagy, a conserved cellular process that maintains homeostasis by degrading unnecessary proteins and dysfunctional organelles. In this study, we report that ATM inhibitors (KU-55933 and KU-60019) provoked accumulation of autophagosomes and p62 and restrained autolysosome formation. Under autophagy-inducing conditions, the ATM inhibitors caused excessive autophagosome accumulation and cell death. This new function of ATM in autophagy was also observed in numerous cell lines. Repression of ATM expression using an siRNA inhibited autophagic flux at the autolysosome formation step and induced cell death under autophagy-inducing conditions. Taken together, our results suggest that ATM is involved in autolysosome formation and that the use of ATM inhibitors in cancer therapy may be expanded.