Fig. 2
From: The independence of and associations among apoptosis, autophagy, and necrosis
Mechanisms of apoptosis. In the exogenous pathway, the binding of FASL, TNF-α, or TRAIL to their corresponding receptors can transform procaspase-8 to caspase-8 through autohydrolysis. In type I cells, activated caspase-8 can activate caspase-3, followed by apoptosis. In type II cells, activated caspase-8 can hydrolyze Bid to tBid, and then tBid interacts with Bax/Bak, which is located on mitochondria, to induce apoptosis. In the intrinsic apoptosis pathway, DNA damage, growth factor withdrawal, oxidative stress, or toxic damage can destroy the homeostasis of the mitochondria, typically controlled by the Bcl-2 family members, and can lead to increased mitochondrial membrane permeability to induce cytochrome c release from the intermembrane space of the mitochondria. In addition, the released cytochrome c can interact with Apaf-1 and caspase-9 to activate caspase-3 and induce apoptosis. In the endoplasmic reticulum stress-induced apoptosis pathway, the disturbance in calcium homeostasis and excessive accumulation of unwanted proteins in the endoplasmic reticulum induce caspase-12-mediated apoptosis, in which activated caspase-12 translocates from the ER into the cytosol to directly cleave caspase-9 and then activate caspase-3
