Fig. 39.
Activation of different death receptor signaling pathways depending on the culture conditions of hepatocytes. In the mouse liver and when kept in suspension right after isolation, hepatocytes undergo apoptosis in response to FasL in a manner dependent on the BH3-only protein Bid and mitochondrial outer membrane permeabilization (cytochrome c release) (so-called type II signaling). However, when plated on a stiff collagen monolayer or embedded into a soft collagen sandwich, the FasL signaling pathway switches to a more direct manner that bypasses mitochondria and cleaves and activates effector caspase-3 directly by death receptor-bound caspase-8 (type I signaling). Interestingly, TNFa signaling does not switch in collagen-cultured hepatocytes, as sensitization of FasL-induced apoptosis by a pretreatment with TNFa remains Bid/mitochondria (type II)-dependent