Maternal organelle contribution to offspring germline health

Project Summary Organelles engage in homeostatic processes to improve cellular health. However, some organelle proteins in the soma can survive many months, making them susceptible to damage during aging. In the germline, gametes can be arrested for a prolonged period before they pass down their organelle content to the next generation. Having damage-prone proteins perdure in the germline would therefore be problematic and challenge the ability of germ cells to pass down healthy material from generation to generation. Upon oocyte maturation and fertilization, certain maternal products are degraded to initiate the maternal to zygotic transition in the developing embryo, though little is known how maternally derived organelles are turned over and replaced with zygotic organelles. Intriguingly, quality control events have been shown to take place in single cell organisms and during asymmetric divisions to ensure the elimination of organelle long-lived proteins (LLPs). However, whether specialized organelle quality control takes places to remove maternally derived LLPs in developing progeny, and how such a process would take place in a multi-cellular organism remains poorly understood. Through molecular and genetic analysis, the research proposed in this fellowship will investigate how maternal organelle input derived from Drosophila oocytes influences germline health of their offspring. First, I will endogenously tag well characterized LLPs to visualize the zygotic pool of proteins along with the maternally derived long-lived pool of the same protein across embryonic, larval and adult progeny. By differentially tagging the maternal and zygotic pool, I will compare protein levels in the progeny germline to assess if it selectively prevents maternally deposited organelle LLPs to be transgenerationally inherited. Next, I will perturb oocyte health to investigate how maternally damaged LLPs contributes to offspring viability. Finally, I will identify additional long-lived proteins that are derived from maternal organelles using a biorthogonal amino acid labeling approach and compare their fates in the progeny germline with well characterized LLPs. The proposed experiments will highlight how maternally derived LLPs impact organelle function in the germline of ensuing progeny. In addition, these studies will shed light on how organelle continuity is maintained between generations and aim to reveal specialized quality control pathways in the germline.