Date of Award
Doctor of Philosophy (PhD)
The nematode C. elegans is a model organism for various biomedical studies due to its genetic simplicity and conservation with humans. As C. elegans is uniquely amenable to cellular, molecular genetic, and biochemical analyses, many basic biological processes are investigated by experimentally manipulating and observing worms. My thesis describes how I used C. elegans models to advance our understanding of paternal mitochondria elimination and cell death regulation.
Mitochondria are membrane-enclosed organelles that carry their own genome (mtDNA). In mammals, the inheritance of mitochondria and mtDNA is strictly maternal, despite the fact that a sperm can inject up to 100 functional mitochondria into the oocyte during fertilization. I report that this paternal mitochondrial elimination process is conserved in C. elegans, and that the autophagy-lysosomal pathway actively participates in this process. A systematic RNA interference screen revealed an endonuclease, CPS-6, that is involved in digesting paternal mtDNA and eliminating paternal mitochondria. Further characterization of paternal mitochondria elimination demonstrates that during fertilization, the mitochondria membrane potential is lost, which might be the initial step for marked destruction of sperm mitochondria.
Using C. elegans to study programmed cell death, or apoptosis, has been extraordinarily effective and productive during the last two decades. However, several key questions remain unsolved. I studied germ cell death initiation by GLA-2. In C. elegans germ lines, how some cells are triggered to "commit suicide" to facilitate peer cells' maturation is poorly understood. I report that GLA-2, the C. elegans homolog of BNIP3, is important in initiating germ cell death. During apoptosis, GLA-2 interacts with the Bcl-2 family protein, CED-9, on the surface of mitochondria and causes translocalization of the Apaf-1 homolog CED-4 to the nucleus and activation of CED-3. In addition, findings suggested that MAP Kinase phosphorylates GLA-2 to regulate its affinity to CED-9 and affect the amount of CED-4 released to modulate the apoptotic process.
Zhou, Qinghua, "Paternal Mitochondria Elimination and Cell Death Regulation in C. elegans" (2012). Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations. 54.