Durgan Joanne, Florey Oliver
Babraham Institute, Signalling Program, Cambridge, UK.
Sci Adv. 2022 Oct 28;8(43):eabo1274. doi: 10.1126/sciadv.abo1274. Epub 2022 Oct 26.
Autophagy is a fundamental catabolic process coordinated by a network of autophagy-related (ATG) proteins. These ATG proteins also perform an important parallel role in "noncanonical" autophagy, a lysosome-associated signaling pathway with key functions in immunity, inflammation, cancer, and neurodegeneration. While the noncanonical autophagy pathway shares the common ATG machinery, it bears key mechanistic and functional distinctions, and is characterized by conjugation of ATG8 to single membranes (CASM). Here, we review the diverse, and still expanding, collection of stimuli and processes now known to harness the noncanonical autophagy pathway, including engulfment processes, drug treatments, TRPML1 and STING signaling, viral infection, and other pathogenic factors. We discuss the multiple associated routes to CASM and assess their shared and distinctive molecular features. By integrating these findings, we propose an updated and unifying mechanism for noncanonical autophagy, centered on ATG16L1 and V-ATPase.
自噬是一种由自噬相关（ATG）蛋白网络协调的基本分解代谢过程。这些ATG蛋白在“非经典”自噬中也发挥着重要的平行作用，“非经典”自噬是一种与溶酶体相关的信号通路，在免疫、炎症、癌症和神经退行性变中具有关键功能。虽然非经典自噬途径共享共同的ATG机制，但它具有关键的机制和功能差异，其特征是ATG8与单膜结合（CASM）。在这里，我们综述了目前已知利用非经典自噬途径的各种且仍在不断扩展的刺激和过程，包括吞噬过程、药物治疗、TRPML1和STING信号传导、病毒感染以及其他致病因素。我们讨论了通往CASM的多种相关途径，并评估它们共同的和独特的分子特征。通过整合这些发现，我们提出了一种以ATG16L1和V-ATP酶为中心的更新的统一非经典自噬机制。
