Dartmouth Medical School geneticists have found links in the cell death machinery of worms and mammals, opening new avenues for studying and targeting a process vital to development and implicated in cancer and autoimmune diseases.
The work, reported in the February 17 issue of Nature, demonstrates the role of mitochondria, the cellular power plant, in prompting worm cells to self destruct. These results unify cell death models along the evolutionary spectrum, from simple animal systems to humans.
In spite of its name, programmed cell death, or apoptosis, is essential for life; it's needed for nervous system development and it keeps the body up and running. Miscues and failures are instrumental in cancer, autoimmune disorders or neurodegenerative diseases.
Mitochondria, the organelles responsible for producing energy to fuel cell processes, also appear to release molecules that set the cell death program in motion. While their activity in mammalian cell death was known, mitochondrial involvement in worms had not previously been shown.
The new work, led by Dr. Barbara Conradt, assistant professor of genetics at Dartmouth Medical School, reveals the importance of mitochondria in cell death in the roundworm C. elegans, enhancing the view of how cell death is conserved from worms to humans.
"Now it seems that there is really one way of killing cells and it involves these mitochondria. Using genetics, we could rigorously show that mitochondria are part of it. It unifies two different hypothesis and makes worms a great model to analyze how cell death is induced, " Conradt said.
Mitochondria are dynamic structures, constantly changing shape, budding and fusing. In cells instructed to die, the mitochondria tend to become smaller or fragment, but whether this fragmentation is a requirement for cell death or a byproduct has been unclear, until now.
Conradt and her colleagues determined that mitochondrial fragmentation is required for cells to die and that the process that commits cells to the point of no return happens quickly. Conradt said it's the clearest confirmation yet that mitochondrial fragmentation is critical in killing cells.
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.