Tasnin Most Naoshia, Takahashi Yuka, Takuma Tsuneyuki, Ushimaru Takashi
Graduate School of Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka, 422-8021, Japan.
Course of Biological Science, Department of Science, Graduate School of Integrated Science and Technology, Shizuoka University, Ohya 836, Suruga-ku, Shizuoka, 422-8021, Japan.
Biochem Biophys Res Commun. 2025 Jan;742:151102. doi: 10.1016/j.bbrc.2024.151102. Epub 2024 Dec 2.
Endosomal sorting complex required for transport (ESCRT) is required for maintenance of nuclear functions and prevention of neurodegenerative diseases. The budding yeast Saccharomyces cerevisiae is an ideal model for studying ESCRT-dependent diseases. Nucleolar proteins are degraded by macronucleophagy and micronucleophagy after nutrient depletion and inactivation of target of rapamycin complex 1 (TORC1) kinase. Here, we show that ESCRT is critical for micronucleophagic degradation of nucleolar proteins upon TORC1 inactivation. In addition, ESCRT was also critical for rDNA condensation and nucleolar remodeling, which is necessary for proper micronucleophagic degradation of nucleolar proteins after TORC1 inactivation. On the other hand, ESCRT was dispensable for bulk macroautophagy, whereas it was also critical for macronucleophagy. Thus, ESCRT has an important role for elimination of nucleolar proteins in response to nutrient deprivation.
转运所需的内体分选复合物(ESCRT)对于维持核功能和预防神经退行性疾病是必需的。出芽酵母酿酒酵母是研究ESCRT依赖性疾病的理想模型。营养物质耗尽和雷帕霉素复合物1(TORC1)激酶失活后,核仁蛋白通过大自噬和微自噬被降解。在此,我们表明ESCRT对于TORC1失活后核仁蛋白的微自噬降解至关重要。此外,ESCRT对于rDNA凝聚和核仁重塑也至关重要,这对于TORC1失活后核仁蛋白的适当微自噬降解是必需的。另一方面,ESCRT对于大量的巨自噬是可有可无的,而它对于大自噬也至关重要。因此,ESCRT在响应营养剥夺时对于消除核仁蛋白具有重要作用。