424C Poster - 05. Reproduction and gametogenesis
Saturday April 09, 1:30 PM - 3:30 PM

Authors:
Yipeng Du; Matthew Sieber

Affiliation: UT Southwestern Medical Center

Keywords:
b. oogenesis; b. oogenesis

Development in all organisms requires the coordination of cellular metabolism with the proper regulation of signaling pathways. For example, changes in mitochondria metabolism have been associated with cell specification and differentiation in many developmental systems. However, despite this association, very little is known about how mitochondrial metabolism regulates developmental pathways. Our lab utilizes Drosophila, mammalian cells, and mice to examine the conserved metabolic mechanisms that drive development and disease progression.
To understand the role for mitochondria in developmental signaling, we conducted a genetic screen of mitochondrial proteins. Using this approach, we discovered that a specific subset of mitochondrial genes, when disrupted, cause defects in development of the Drosophila ovary and intestine. In particular, we found that inhibition of prohibitin (PHB in mammals) in germ cells caused a block in follicle cell differentiation. Loss of prohibitin in the mitochondria causes: a reduction of membrane potential, decreased ATP production, and increased cellular ROS. These defects in mitochondrial oxidative metabolism cause an increase in follicle cell number, reduced size of follicle cell nuclei, and defects in follicle cell differentiation in prohibitin RNAi egg chambers. When we examine the localization of the Notch ligand, Delta, we find that it accumulates in large puncta in prohibitin RNAi egg chambers and fails to reach the plasma membrane. Interestingly, lowering ROS by overexpression Catalase and Sod2 genes partially rescue the Delta aggregation developmental phenotypes in ovaries. In addition, we have found that overexpression of Rab11 which is a key protein of recycling vesicles rescue the phenotype of Delta aggregation in prohibitin RNAi egg chambers. These data suggest that mitochondrial ROS regulates Delta trafficking in Rab11 dependent manner. Overall, our work provides intriguing new evidence that identifies the regulation of receptor trafficking as a novel mechanism for how mitochondria regulate differentiation. Moreover, this work provides a foundation for future studies of how changes in mitochondria metabolism promotes cancer progression by regulating Notch signaling.