Fate decisions mediated by crosstalk of autophagy and apoptosis in mammalian cells

Abstract

Autophagy is an important cell activity which is the process of formation of autophagosomes, docking with lysosomes and degradation. The intrinsic pathway of apoptosis involves mitochondrial outer membrane permeabilization (MOMP) and cytochrome c release followed by caspase activation. Many molecules, e.g., Ca 2+ and mTOR, and different stresses such as endoplasmic reticulum (ER) stress and nutritional stress take part in these two processes. However, the mechanism of how they work together so as to determine cell fate decisions remains to be clarified. Here, we present a computational model for cell fate decisions based on intertwined dynamics with autophagy and apoptosis involving Ca 2+ , mTOR, and both ER stress and nutritional stress. In agreement with experimental observations, the model predicts that both Ca 2+ and the stresses play critical roles in regulating the choice between autophagy and apoptosis in a combinatorial way. The model presented here might be a good candidate for providing the qualitative mechanism of cell fate decisions mediated by Ca 2+ , mTOR, and two kinds of stress.

Neuroprotective and anti-epileptic potentials of genus Artemisia L.

“…The Bcl-2 family is a well-characterized protein family involved in the modulation of apoptotic cell death, consisting of anti-apoptotic Bcl-2 protein and pro-apoptotic Bax and Bak, which are key modulators of the intrinsic (mitochondrial) pathway of apoptosis. Under normal conditions, Bcl-2, which localizes to the outer mitochondrial membrane, promotes cell survival by inhibiting Bax/Bak oligomerization, which would otherwise facilitate the release of cytochrome c from mitochondria ( Ge and Wang, 2020 ). In response to cellular stress, Bax/Bak oligomers create pores in the mitochondrial outer membrane, leading to depolarization of the mitochondrial membrane potential (ΔΨm) and release of cytochrome c into the cytoplasm ( Ly, Grubb and Lawen, 2003 ; Westphal et al, 2011 ).…”

“…Seizure-induced stress on neurons enhances accumulation of mitochondrial Ca 2+ , which can not only further stimulate overproduction of ROS, but also facilitate the release of cytochrome c from the mitochondria to cytosol, triggering caspase-3-dependent neural apoptosis ( Fricker et al, 2018 ; Ge and Wang, 2020 ).…”

Neuroprotective and Anti-Epileptic Potentials of Genus Artemisia L.

“…Cytosolic cytochrome c further activates caspases and leads to cell apoptosis [49]. In contrast, Bcl-2 binds/inactivates Bax and prevents Bax/Bak oligomerization, which would otherwise cause the mitochondrial release of cytochrome c and several other apoptotic molecules [51] Recently, various studies have documented the neuroprotective and antiapoptotic effects of Artemisia. The ethanol extract of Artemisia judaica increased the level of the antiapoptotic marker Bcl2 and decreased the level of the pro-apoptotic marker Bax by blocking the neuronal apoptosis induced by injection of STZ into the rat brain [32].…”