In prophase of the first meiotic division, chromatin forms a compact spherical cluster called the karyosome within the enlarged oocyte nucleus in Drosophila melanogaster. Similar clustering of chromatin has been widely observed in oocytes in many species including humans. It was previously shown that the proper karyosome formation is required for faithful chromosome segregation, but knowledge about its formation and maintenance is limited. To identify genes involved in karyosome formation, we carried out a large-scale cytological screen using Drosophila melanogaster oocytes. This screen comprised 3916 genes expressed in ovaries, of which 106 genes triggered reproducible karyosome defects upon knockdown. The karyosome defects in 24 out of these 106 genes resulted from activation of the meiotic recombination checkpoint, suggesting possible roles in DNA repair or piRNA processing. The other genes identified in this screen include genes with functions linked to chromatin, nuclear envelope, and actin. We also found that silencing of genes with mitochondrial functions, including electron transport chain components, induced a distinct karyosome defect typically with de-clustered chromosomes located close to the nuclear envelope. Furthermore, mitochondrial dysfunction not only impairs karyosome formation and maintenance, but also delays synaptonemal complex disassembly in cells not destined to become the oocyte. These karyosome defects do not appear to be mediated by apoptosis. This large-scale unbiased study uncovered a set of genes required for karyosome formation and revealed a new link between mitochondrial dysfunction and chromatin organization in oocytes.

在第一次减数分裂的前期，染色质在果蝇增大的卵母细胞核内形成一个紧凑的球形簇，称为核体。在包括人类在内的许多物种的卵母细胞中，广泛观察到类似的染色质聚集。之前的研究表明，正确的核体形成是染色体忠实分离所必需的，但对其形成和维持的了解有限。为了鉴定参与核体形成的基因，我们使用果蝇进行了大规模细胞学筛选卵母细胞。该筛选包含 3916 个在卵巢中表达的基因，其中 106 个基因在敲低后触发可重现的核体缺陷。这 106 个基因中有 24 个的核体缺陷是由减数分裂重组检查点的激活引起的，表明可能在 DNA 修复或 piRNA 加工中发挥作用。此筛选中鉴定的其他基因包括具有与染色质、核膜和肌动蛋白相关的功能的基因。我们还发现，具有线粒体功能的基因（包括电子传递链成分）的沉默会诱导明显的核体缺陷，通常导致靠近核膜的染色体去簇。此外，线粒体功能障碍不仅损害核体的形成和维持，而且还延迟注定不会成为卵母细胞的细胞中联会复合体的分解。这些核体缺陷似乎不是由细胞凋亡介导的。这项大规模、公正的研究发现了核体形成所需的一组基因，并揭示了线粒体功能障碍与卵母细胞染色质组织之间的新联系。