The Mitochondrial Protein Cytochrome c heme lyase is Necessary for Cell Polarity. Sarah E. Kleinsorge, Caryn Navarro. Graduate Program in Genetics and Genomics, BUSM, Boston, MA.

   In Drosophila, the oocyte is specified and maintained through the asymmetric localization of cell cycle and cell polarity RNAs, proteins, and organelles such as mitochondria to and within the oocyte. We performed an EMS mutagenesis screen in Drosophila to uncover new genes important for cell polarity establishment and oocyte development. We discovered that one of the mutant lines isolated in the screen had a mutation in the highly conserved catalytic domain of the nuclear encoded mitochondrial protein Cytochrome c heme lyase (Cchl). In organisms such as humans, mice and flies all embryonic mitochondria are maternally inherited from the oocyte. However, the role of mitochondrial function in oocyte development is currently unknown. We therefore went on to characterize Cchl function during drosophila oogenesis. In Cchl mutant oocytes, cell polarity is initially established but not maintained. Cchl is known to function in the electron transport chain (ETC) to maintain proper ATP levels. In support of Cchl functioning in the ETC to maintain oocyte polarity we find that mutations in other genes necessary for ETC function show a similar phenotype as Cchl mutant oocytes. Therefore, we hypothesize that in Cchl mutant oocytes the energy level in the cell may not be high enough to maintain the processes leading to proper oocyte specification, such as dynein-mediated microtubule motor transport. However, the ETC also produces second messengers such as reactive oxygen species, calcium and ATP and these signals may trigger downstream pathways that are necessary to maintain oocyte polarity. Our current work focuses on determining which of these hypotheses are correct. Since the Cchl protein is both structurally and functionally conserved between flies and mammals, these studies could further our understanding of premature ovarian failure and reproductive ageing.