Quantitative indices of autophagy activity from minimal models

A number of cellular- and molecular-level studies of autophagy assessment have been carried out with the help of various biochemical and morphological indices. Still there exists ambiguity for the assessment of the autophagy status and of the causal relationship between autophagy and related cellular changes. To circumvent such difficulties, we probe new quantitative indices of autophagy which are important for defining autophagy activation and further assessing its roles associated with different physiopathological states.

Our approach is based on the minimal autophagy model that allows us to understand underlying dynamics of autophagy from biological experiments. Specifically, based on the model, we reconstruct the experimental context-specific autophagy profiles from the target autophagy system, and two quantitative indices are defined from the model-driven profiles. The indices are then applied to the simulation-based analysis, for the specific and quantitative interpretation of the system.

Two quantitative indices measuring autophagy activities in the induction of sequestration fluxes and in the selective degradation are proposed, based on the model-driven autophagy profiles such as the time evolution of autophagy fluxes, levels of autophagosomes/autolysosomes, and corresponding cellular changes. Further, with the help of the indices, those biological experiments of the target autophagy system have been successfully analyzed, implying that the indices are useful not only for defining autophagy activation but also for assessing its role in a specific and quantitative manner.

Such quantitative autophagy indices in conjunction with the computer-aided analysis should provide new opportunities to characterize the causal relationship between autophagy activity and the corresponding cellular change, based on the system-level understanding of the autophagic process at good time resolution, complementing the current in vivo and in vitro assays.