Abstract
Extensive studies performed in the last 10 years have unveiled a considerable amount of the molecular basis of apoptosis. Mitochondrial membrane permeabilization is one of the most critical events in apoptosis in mammals, because it leads to the release of apoptogenic factors, including cytochrome c, into the cytoplasm, which activates death-executing programs including caspases. The Bcl-2 family of proteins, consisting of anti-apoptotic and pro-apoptotic members, directly controls mitochondrial membrane permeability. Pro-apoptotic members of the family participate in sensing/transmitting apoptotic signals to the mitochondria, as well as permeabilization of mitochondiral membrane. We have been studying the molecular basis of function of Bcl-2 family proteins, as well as various aspects of apoptotic signaling and execution. In this symposium, I will focus particularly on the signaling pathway of DNA double strand break-induced apoptosis. We have been attempting to identify a molecule, which appears in the cytoplasm upon DNA double strand breaks and has a cytochrome c-releasing activity. By introducing our recent data, I will discuss how DNA double strand breaks trigger apoptotic signals, which are transmitted to the mitochondria and induce membrane permeabilization. [J Radiat Res 44:377 (2003)]
