ABSTRACT
It is now well-established that the energy requirement of a cell is significantly increased during DPCI in the most vulnerable cells. These deleterious events induce ER and mitochondrial oxidative stress to accelerate ATP synthesis. Free radicals are generated as a byproduct of mitochondrial oxidative phosphorylation during ATP synthesis in the electron transport chain. Free radicals are highly unstable reactive oxygen and nitrogen species (such as ·OH, CO·, and NO·). Particularly, ONOO– ions are highly deleterious and are synthesized by the Fenton reaction from ·OH and NO· in the presence of iron. ONOO– ions not only induce oxidative but also nitrative stress to cause degeneration of mitochondrial membranes. Thus, free radical-induced CMB triggers CB formation to prevent dissemination of highly toxic mitochondrial metabolites as an initial attempt of ICD. CB is eliminated from the intracellular compartment by an ATP-driven charnolophagy (CB autophagy), resulting in the formation of a CPS. The CPS is subsequently transformed to CS when the phagocytosed CB is hydrolyzed by the lysosomal enzymes.
