Novel functions of mitochondrial proteins in chromosome segregation during meiosis and mitosis

The original concept of this project stemmed from a desire to take a molecular biology approach to seek potential drug targets to cure the parasitic disease Schistosomiasis. The initial work involved, selection of the inner mitochondrial membrane protein prohibitin using Caenorhabditis elegans as a model system. In this model, targeting this protein that was conserved in both C. elegans and Schistosomes should cause embryonic lethality. Surprisingly, RNAi of this protein did cause embryonic lethality, in C. elegans, but because of its conserved nature, prohibitin appeared not to be a potential drug target, so we then set out on the different task of determining a method action. Subsequent experiments demonstrated that depletion of not just prohibitin, but numerous other mitochondrial proteins resulted in high incidences of embryonic lethality. In addition, depletion of these proteins caused meiotic and mitotic defects in the developing embryo. More specifically, depletion of subunits of complex II of the Electron Transport Chain (ETC) subunit Succinate Dehydrogenase caused a specific 2--4 cell early embryonic arrest, coupled with defects in centrosome duplication. In an effort to determine what processes the mitochondria proteins were involved, suppression experiments were performed to determine if certain mutant strains could rescue the embryonic lethality that has been previously described. Interestingly, mutants involved in processes such as insulin signaling, cellular detoxification mechanisms, and cell cycle checkpoints were able to suppress the embryonic lethality that occurs when mitochondrial proteins are depleted. The following dissertation describes novel processes of mitochondrial proteins outside of the mitochondria.