Apoptotic and necrotic cell death induced by death domain receptors.
Apoptosis and necrosis are two distinct forms of cell death. Caspases are indispensable as initiators and effectors of apoptotic cell death and are involved in many of the morphological and biochemical features of apoptosis. Major changes in mitochondrial membrane integrity and release of proapoptotic factors, such as cytochrome c from the mitochondrial intermembrane space, play an important sensor and amplifying role during apoptotic cell death. In vitro studies of cell death in cell lines have revealed that inhibition of the classical caspase-dependent apoptotic pathway leads in several cases to necrotic cell death. Thus, the same cell death stimulus can result either in apoptotic or necrotic cell death, depending on the availability of activated caspase. Therefore, death domain receptors may initiate an active caspase-independent necrotic signaling pathway. In this review, we describe what is known about the apoptotic and necrotic cell death pathways. Principal elements of necrosis include mitochondrial oxidative phosphorylation, reactive oxygen production, and non-caspase proteolytic cascades depending on serine proteases, calpains, or cathepsins.
Denecker
G
G
Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology and University of Ghent, Belgium.
Vercammen
D
D
Declercq
W
W
Vandenabeele
P
P
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism / Q000502:physiology*; D004789:Enzyme Activation; D053200:Fas-Associated Death Domain Protein; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D009336:Necrosis; D011506:Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism / Q000502:physiology*; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D015398:Signal Transduction; D047990:TNF Receptor-Associated Factor 1
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D047990:TNF Receptor-Associated Factor 1; C506249:RIPK1 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D020169:Caspases