The Oscillation Amplitude, Not the Frequency of Cytosolic Calcium, Regulates Apoptosis Induction

We will discuss about “The Oscillation Amplitude, Not the Frequency of Cytosolic Calcium, Regulates Apoptosis Induction ”, Qi et al., iScience, 2020

Abstract:

Although a rising concentration of cytosolic Ca²⁺ has long been recognized as an essential signal for apoptosis, the dynamical mechanisms by which Ca²⁺ regulates apoptosis are not clear yet. To address this, we constructed a computational model that integrates known biochemical reactions and can reproduce the dynamical behaviors of Ca²⁺-induced apoptosis as observed in experiments. Model analysis shows that oscillating Ca²⁺ signals first convert into gradual signals and eventually transform into a switch-like apoptotic response. Via the two processes, the apoptotic signaling pathway filters the frequency of Ca²⁺ oscillations effectively but instead responds acutely to their amplitude. Collectively, our results suggest that Ca²⁺ regulates apoptosis mainly via oscillation amplitude, rather than frequency, modulation. This study not only provides a comprehensive understanding of how oscillatory Ca²⁺ dynamically regulates the complex apoptotic signaling network but also presents a typical example of how Ca²⁺ controls cellular responses through amplitude modulation.