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在蛋白质毒性应激过程中,TOR和热冲击反应途径调节过氧体生物发生
Nandini Shukla1,2, Maxwell L Neal3, Jean-Claude Farré4
1Department of Molecular Biology, School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA. nandini.shukla@unt.edu.
Nature communications
|November 29, 2025
概括
细胞蛋白质毒性压力通过增加生物生成触发过氧体增殖,有助于恢复. 这种保存反应涉及热冲击激活和目标拉帕米辛 (TOR) 抑制.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 有机体动力学 有机体动力学
背景情况:
- 过氧体是重要的器官,参与能量恒温和氧化还原平衡.
- 过氧体功能障碍与各种疾病有关,但它们在细胞压力下的动态调节尚未得到充分理解.
研究的目的:
- 研究在蛋白质毒性压力期间控制氧体动态的机制.
- 确定过氧体生物发生在细胞从蛋白质毒性压力中恢复的作用.
主要方法:
- 利用酵母模型研究过氧体对各种蛋白质毒性压力条件的反应.
- 通过新生生物生成,生长和分裂分析过氧化体的增殖,与食形成对比.
- 研究的信号通路包括热冲击反应和拉巴胺素 (TOR) 信号的目标.
- 在人类纤维细胞中得到验证的发现.
主要成果:
- 蛋白质毒性压力,包括ER或细胞间伴侣功能障碍,蛋白质转位受损,糖化中断或还原性压力,诱导过氧体增殖.
- 过氧酶体的增殖是通过从ER增强的de novo生物发生,生长和分裂而不是减少食.
- 过氧体生物生成对于细胞从蛋白质毒性压力中恢复至关重要.
- 这种反应是由热冲击路径激活和TOR信号抑制介导的.
- 在人类细胞中也观察到类似的效应.
结论:
- 过氧体在细胞对蛋白质毒性压力的反应中起着关键和保存的作用.
- 增强的过氧体生物发生是一种关键的适应机制,用于在压力下维持细胞平衡.
- 向过氧体动态可能为与蛋白质毒性压力相关的疾病提供治疗策略.
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