( required for cells to die and that the ...)Critical role in programmed cell death identified

C. elegans worms are a convenient model system, Conradt explained, with a well documented cell lineage that facilitates genetic manipulation. Their cell death machinery is simple, with one component for each of the different factors involved in the central cell killing apparatus. Mammals on the other hand have multiple components or families of proteins for these factors; moreover, their cell death is more sporadic and harder to pinpoint.

In worms, scientists know exactly which cells are dying, and when and where. During development, 1,090 cells form, but 131 of these cells die; the same cells always die at the same time and at the same place. This feature makes it possible to identify mutant worms, in which cells that should have died instead live. Worms whose cell death program is blocked survive, at least in the lab, with their 131 extra cells. Such studies are impractical in mammals because cell death is essential and animals with a cell death defect die.

The researchers demonstrated that when they cause worm mitochondria to fragment without instructing cells to die, the cells still die and when they block fragmentation, the cells survive; in other words, blocking fragmentation prevents cell death, inducing fragmentation provokes cell death.

"This programmed cell death is so important and the more players we know that are involved, the more potential targets we have for therapeutics," Conradt said. During development, for example, many neurons are built, but after birth, more than half are eliminated in the central nervous system in mammals: "It's a common safeguard, to ensure that neurons talk to the right neighbors and make the right connections." Also, if cells do not die on schedule, unregulated growth can lead
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Source:Dartmouth Medical School