Deleterious network hypothesis of apoptosis.

Apoptosis or programmed cell death (PCD) plays crucial roles in a number of physiological and pathological processes. Growing evidence has suggested that oxidative damage, altered calcium homeostasis and abnormal mitochondrial functions are three key factors of PCD. Because a number of studies have also indicated that a deleterious network is formed on the basis of the close interactions among these major apoptotic factors, it is proposed that the deleterious network is just the common pathway in PCD. A variety of apoptotic stimuli can trigger the network, leading to the characteristic apoptotic changes. This new theory--the deleterious network hypothesis of apoptosis--appears to unify some major theories of PCD, providing consistent explanations of a significantly larger number of the observations about apoptosis than other hypotheses. Based on this unifying hypothesis, it is suggested that the three major factors of the deleterious network could be targeted for treatment of multiple apoptosis-related disorders.