37.7: Autophagic Cell Death
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic protein, Bax is bound to anti-apoptotic protein Bcl-2. Under stress, Bcl-2 is moderately phosphorylated, and Beclin-1 is released to activate autophagy. If the phosphorylation is intense, then Bax is released, leading to the activation of apoptosis. Autophagy can initiate necroptosis when the autophagosomes and autolysosomes are degraded.
In some cases, sodium potassium ATPase binds to Beclin-1 and induces autosis. Autosis is a type of cell death induced by an increased rate of non-apoptotic autophagy. It causes upregulation of rubicon protein which prevents fusion between autophagosomes and lysosomes. This results in the excessive accumulation of autophagosomes inside the cell, leading to its death.
