Speaker
Description
This research investigates the dynamic interplay between energy metabolism and protein homeostasis (proteostasis) under conditions of energetic stress. We present a two state kinetic model that tracks how proteins transition between unfolded and native conformations through synthesis, folding, unfolding, and degradation. This framework captures both transient and steady state behavior of the protein pool, allowing us to identify biologically realistic parameter ranges to establish baseline mechanisms and parameter bounds. We explore different kinetic assumptions, such as linear, nonlinear, and Michaelis–Menten forms to determine how they affect stability, with a key focus on identifying conditions under which the system becomes unstable, as an overload of unfolded proteins is expected to drive proteostatic collapse. We will also discuss how we are extending this preliminary model by introducing an aggregation state to better reflect the proteostasis mechanisms. Comparing the two and three state models will enable us to evaluate whether aggregation acts as a stabilizing or destabilizing force. We first establish proteostasis baselines before adding energetics, revealing whether instability arises internally or from energy limits. Together, these results define theoretical boundaries between resilience and collapse, providing mechanistic insight into stress responses across molecular and cellular scales.
