Biochemical determinants of apoptosis and necrosis

Although apoptosis and necrosis were originally thought to be entirely distinct mechanisms of cell death, recent work has shown that the processes are regulated by many of the same biochemical intermediates, most notably the levels of cellular ATP, Ca2+, reactive oxygen species, and thiol antioxidants. Beyond a certain threshold, it appears that stress-induced changes in these modulators 'switches' the cell death mechanism from apoptosis to necrosis. Importantly, even when this occurs, cell death can be attenuated by bcl-2 and caspase inhibitors, which are known for their abilities to block apoptosis. This review will summarize these observations within the context of what is currently known about the effector machinery for apoptotic cell death, and possible mechanistic explanations for the switch between apoptosis and necrosis will be provided.