The 'Upstairs/Downstairs' Mystery Of Cell Suicide Is Burdened By Too Much Evidence

Mitochondria are sacs of enzymes in the cell that extract energyfrom food and store this energy in the high-powered chemical bonds ofmolecules called ATP. Virtually all activity of cells requires energysupplied by ATP, which acts as the "currency" with which the cell"buys" chemical reactions.

The fact that more than 100,000 research papers on apoptosis have beenpublished is ironic, since this vast amount of information contributesto the confusion over which signaling pathways are most important fortriggering this process, according to Douglas R. Green, Ph.D., chair ofImmunology at St. Jude and holder of the Peter C. Doherty Endowed Chairof Immunology. Green is senior author of an editorial on apoptosis thatappears in the October 7 issue of Science.

Apoptosis is the orderly process that both sculpts developing organismsout of a mass of replicating cells and disposes of irreparably damaged,mutated or infected cells. For example, cells that suffer DNA mutationsthat cannot be repaired undergo apoptosis to prevent them from forminga tumor.

Understanding the fine points of apoptosis is important to researchersseeking ways to control this process, Green said. Among the manytherapeutic applications of such control would be triggering cancercells to commit suicide. "But we can't design definitive treatmentsuntil we understand which pathways leading to apoptosis are the mostimportant," Green said.

The major event in apoptosis is the breakdown of the membranes of themitochondria. This breakdown allows certain proteins to spill out ofthe mitochondrion and help form a suicide switch called the apoptosome.Some of the critical steps in apoptosis occur before that breakdown ofthe mitochondria, that is, "upstairs" from the mitochondria, Greensaid. The other critical steps occur after, or "downstairs" from themitochondria, he added.

"Based on all the information available, you could conclude that anenormous number of molecules and pathways trigger apoptosis," Greennoted. "So we need to identify the most important series of steps inthis process. Otherwise we might concentrate too much of our attentionon relatively unimportant byways on the road to apoptosis and miss themajor highways."

The other authors of this paper include Diana Spierings, Gavin McStay,Maya Saleh, Cheryl Bender and Uli Maurer (La Jolla Institute) and JerryChipuk (St. Jude).

St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is internationally recognized forits pioneering work in finding cures and saving children with cancerand other catastrophic diseases. Founded by late entertainer DannyThomas and based in Memphis, Tenn., St. Jude freely shares itsdiscoveries with scientific and medical communities around the world.No family ever pays for treatments not covered by insurance, andfamilies without insurance are never asked to pay. St. Jude isfinancially supported by ALSAC, its fund-raising organization.