Scientists at St. Jude Children's Research Hospital have demonstrated that a key event during apoptosis (cell suicide) occurs as a single, quick event, rather than as a step-by-step process. Apoptosis eliminates extraneous cells from the developing body; and disposes of cells that sustain irreparable harm to their DNA or are infected with microorganisms. The researchers photographed individual cells undergoing that process, allowing investigators to observe the release of certain proteins from pores in the membranes of mitochondria. These cellular structures contain enzymes that extract energy from food molecules, and the space within the membrane surrounding them holds a variety of proteins that are released during apoptosis.
Results of the study indicate the formation of pores in the mitochondrial membranes is a rapid process that allows a nearly simultaneous rather than a sequential release of many apoptosis proteins, according to Douglas Green, Ph.D., chair of the St. Jude Department of Immunology. Green is senior author of a report on this work that appears in the August 1 issue of Proceedings of the National Academy of Sciences. The process of pore formation, called mitochondrial outer membrane permeabilization (MOMP), allows apoptosis proteins stored underneath the membrane to escape and orchestrate the cell's destruction.
MOMP is controlled by a family of proteins called Bcl-2; some of these support apoptosis and others interrupt the process. The pro- and anti-apoptotic Bcl-2 proteins cooperate to weigh and balance cell signals that promote survival or death, in this way determining the final outcome. During apoptosis, these proteins are either already on the mitochondrial membranes or migrate to the membranes, where they trigger MOMP.
"The slow, continuous release of one of the proteins, apoptosis-inducing factor (AIF), suggests that the pore formed during MOMP remains open for many hours," Green said. "Our finding of nearly simulta
Contact: Bonnie Kourvelas
St. Jude Children's Research Hospital