Maternal organelle contribution to offspring germline health

项目摘要 细胞器参与动态平衡过程，以改善细胞健康。然而，一些细胞器蛋白质在 胞体可以存活数月，这使得它们在老化过程中容易受到损害。在生殖系中，配子 在它们将细胞器内容传给下一代之前，它们可能会被长期滞留。 因此，在生殖系中保持易损伤的蛋白质将是有问题的，并挑战这种能力 将健康的物质代代相传。在卵母细胞成熟和 受精，某些母体产物在发育过程中被降解以启动母体向合子的转变 胚胎，尽管鲜为人知的是母体来源的细胞器是如何被合子所取代的 细胞器。有趣的是，质量控制事件已被证明发生在单细胞生物体中，并在 不对称分裂以确保消除细胞器长寿命蛋白(LLP)。然而，无论是 专门的细胞器质量控制在发育后代中去除母体来源的LLP，以及 这样的过程如何在多细胞生物体中发生仍然知之甚少。通过分子 和遗传分析，这项在该奖学金中提出的研究将调查母体细胞器输入 来源于果蝇卵母细胞会影响其后代的种系健康。首先，我会内生标记好 特征化的LLP以可视化合子蛋白质池以及母体来源的长寿池 在胚胎、幼虫和成体后代中都有相同的蛋白质。通过对母体和受精卵进行差异标记 我将比较后代生殖系中的蛋白质水平，以评估它是否选择性地防止母体沉积 细胞器LLP可跨代遗传。接下来，我将扰动卵母细胞健康来调查母体是如何 受损的LLP有助于后代的生存能力。最后，我将识别其他长寿蛋白质，这些蛋白质 用双正交氨基酸标记方法从母体细胞器中提取并比较它们在 具有良好LLP特性的后代生殖系。拟议中的实验将强调母性 衍生的LLP影响后代种系的细胞器功能。此外，这些研究将使 阐明细胞器如何在世代之间保持连续性，并旨在揭示专门的质量控制 生殖系中的路径。

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.