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

Abstract

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.