研究动态
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让我们来谈谈通量:自噬率测量在疾病中的潜力不断上升。

Let's talk about flux: the rising potential of autophagy rate measurements in disease.

发表日期:2024 Jul 10
作者: Nitin Sai Beesabathuni, Matthew W Kenaston, Ritika Gangaraju, Neil Alvin B Adia, Vardhan Peddamallu, Priya S Shah
来源: Autophagy

摘要:

巨自噬/自噬越来越多地与多种疾病相关,使其成为有吸引力的治疗靶点。然而,自噬的许多方面尚未完全了解,其对许多疾病的影响仍然存在争议且因情况而异。在这些情况下缺乏系统和动态的测量是造成这种模糊性的一个关键原因。近年来,Loos 等人。 2014 年和 Beesabathuni 等人。 2022 开发了全面定量测量自噬的方法。在这篇评论中,我们提出了一些有关自噬的未解决的生物学问题,并考虑了定量测量如何解决这些问题。虽然应用范围不断扩大,但我们提供了癌症、病毒感染和机械筛查方面的具体用例。我们阐述了速率测量本身如何成为开发癌症疗法的核心,并提出了利用这些工具来剖析病毒自噬相互作用的复杂性的方法。筛选方法可以与速率测量相结合,以机械方式破译癌症和病毒感染中自噬调节的迷宫。总而言之,这些方法有可能阐明各种疾病的潜在机制。缩写 MAP1LC3/LC3:微管相关蛋白 1 轻链 3; R1:自噬体形成率; R2:自噬体-溶酶体融合率; R3:自溶酶体周转率。
Macroautophagy/autophagy is increasingly implicated in a variety of diseases, making it an attractive therapeutic target. However, many aspects of autophagy are not fully understood and its impact on many diseases remains debatable and context-specific. The lack of systematic and dynamic measurements in these cases is a key reason for this ambiguity. In recent years, Loos et al. 2014 and Beesabathuni et al. 2022 developed methods to quantitatively measure autophagy holistically. In this commentary, we pose some of the unresolved biological questions regarding autophagy and consider how quantitative measurements may address them. While the applications are ever-expanding, we provide specific use cases in cancer, virus infection, and mechanistic screening. We address how the rate measurements themselves are central to developing cancer therapies and present ways in which these tools can be leveraged to dissect the complexities of virus-autophagy interactions. Screening methods can be combined with rate measurements to mechanistically decipher the labyrinth of autophagy regulation in cancer and virus infection. Taken together, these approaches have the potential to illuminate the underlying mechanisms of various diseases.Abbreviation MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; R1: rate of autophagosome formation; R2: rate of autophagosome-lysosome fusion; R3: rate of autolysosome turnover.