Mitochondrial dynamics in Caenorhabditis elegans programmed cell death

As multicellular organisms appeared in evolution, about 1.5 billion
years ago, a process called programmed cell death or apoptosis
evolved. Genetic studies of physiological cell death in the
nematode Caenorhabditis elegans have elucidated a molecular model
of the central cell death machinery consisting of the genes egl-1,
ced-9, -4 and -3. Remarkably, considering C. elegans evolutionarily
separated from mammals millions of years ago, this pathway appears
to be highly conserved from the nematode to humans. However, unlike
in mammals, even though egl-1, ced-4 and -9 appear to localize to
the mitochondrion in vivo there has been very little evidence to
date that mitochondria play any role in the induction of C. elegans
physiological cell death. This investigation demonstrates that
mitochondria fragment upon induction of cell death and that this
mitochondrial morphological change is not seen in egl-1 and ced-9
mutants but in ced-4 and -3 mutants. This genetic analysis suggests
that mitochondrial division is an active process that occurs before
caspase activation. Furthermore, the mitochondrial fragmentation
event is both required and sufficient for physiological cell death
in C. elegans. In conclusion, this work supports an important role
of mitochondria in the execution of programmed cell death,
suggesting that the evolutionary conservation from worm to man is
stronger than previously assumed.