STUDY OF APOPTOSIS IN VITRO CELL-FREE SYSTEM

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Apoptosis is an important suicide program involved in a variety of biological phenomena including morphogenesis and maintenance of tissue homeostasis. Apoptosis is an important theme not only in biology but also in medical field because dysregulation of apoptosis leads to various diseases such as cancer and Alzheimer's disease. However, the molecular basis of apoptosis is still largely unknown. We have been studying ICE family proteases with apoptosis-driving activity and bcl-2 family with anti-apoptotic activity. For detailed study of the function of known genes involved in apoptosis and also for identification of new apoptosis-related genes, in vitro apoptosis system would be extremely useful. Although one system originally developed by Y.Lazebnik has been widely used, we have developed a new system which resembles much better in vivo apoptosis than Lazebnik's system.Recently we have shown that mitochondrial dysfunction through membrane potential loss which is inhibited by Bcl-2, plays an important role in apoptosis. To analyze the biochemical basis of Bcl-2 anti-apoptotic function, we have established a system with isolated mitochondria in which Bcl-2 functions to prevent membrane potential loss.These systems would be very useful for study of molecular basis of apoptosis, and likely provide new insights into control of diseases developing though deregulation of apoptosis.