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Jagasia, Ravi (2005): Mitochondrial dynamics in Caenorhabditis elegans programmed cell death. Dissertation, LMU München: Fakultät für Biologie



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.