Oscillation of Autophagy Induction under Cellular Stress and What Lies behind It, a Systems Biology Study.

ABSTRACT: One of the main inducers of autophagy-dependent self-cannibalism, called ULK1, is tightly regulated by the two sensor molecules of nutrient conditions and energy status, known as mTOR and AMPK kinases, respectively. Recently, we developed a freely available mathematical model to explore the oscillatory characteristic of the AMPK-mTOR-ULK1 regulatory triangle. Here, we introduce a systems biology analysis to explain in detail the dynamical features of the essential negative and double-negative feedback loops and also the periodic repeat of autophagy induction upon cellular stress. We propose an additional regulatory molecule in the autophagy control network that delays some of AMPK's effect on the system, making the model output more consistent with experimental results. Furthermore, a netw

SUBMITTER: Hajdu B 

PROVIDER: S-EPMC10143760 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature