Graduate School of Science and Technology, Shizuoka University, Shizuoka, Japan.
Course of Biological Science, Department of Science, Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka, Japan.
J Cell Biol. 2018 Aug 6;217(8):2675-2690. doi: 10.1083/jcb.201706164. Epub 2018 Jun 29.
Nutrient starvation or inactivation of target of rapamycin complex 1 (TORC1) in budding yeast induces nucleophagy, a selective autophagy process that preferentially degrades nucleolar components. DNA, including ribosomal DNA (rDNA), is not degraded by nucleophagy, even though rDNA is embedded in the nucleolus. Here, we show that TORC1 inactivation promotes relocalization of nucleolar proteins and rDNA to different sites. Nucleolar proteins move to sites proximal to the nuclear-vacuolar junction (NVJ), where micronucleophagy (or piecemeal microautophagy of the nucleus) occurs, whereas rDNA dissociates from nucleolar proteins and moves to sites distal to NVJs. CLIP and cohibin, which tether rDNA to the inner nuclear membrane, were required for repositioning of nucleolar proteins and rDNA, as well as effective nucleophagic degradation of the nucleolar proteins. Furthermore, micronucleophagy itself was necessary for the repositioning of rDNA and nucleolar proteins. However, rDNA escaped from nucleophagic degradation in CLIP- or cohibin-deficient cells. This study reveals that rDNA-nucleolar protein separation is important for the nucleophagic degradation of nucleolar proteins.
营养饥饿或雷帕霉素靶蛋白复合物 1（TORC1）在 budding 酵母中的失活诱导核噬作用，这是一种选择性自噬过程，优先降解核仁成分。尽管 rDNA 嵌入核仁中，但 DNA（包括核糖体 DNA（rDNA））不会被核噬作用降解。在这里，我们表明 TORC1 失活促进核仁蛋白和 rDNA 向不同部位的重新定位。核仁蛋白移动到靠近核-液泡连接（NVJ）的部位，在这里发生微核噬作用（或核的分段微自噬），而 rDNA 从核仁蛋白解离并移动到 NVJ 远端的部位。CLIP 和 cohibin 将 rDNA 固定在内核膜上，对于核仁蛋白和 rDNA 的重新定位以及核仁蛋白的有效核噬作用降解是必需的。此外，微核噬作用本身对于 rDNA 和核仁蛋白的重新定位是必要的。然而，在 CLIP 或 cohibin 缺陷细胞中，rDNA 逃避了核噬作用降解。这项研究揭示了 rDNA-核仁蛋白分离对于核仁蛋白的核噬作用降解很重要。
