在细胞刺激和应激条件下,α-synuclein调节线粒体Ca2+从ER吸收
Meraj Ramezani1, Alice Wagenknecht-Wiesner1, Tong Wang1
1Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14853, USA.
NPJ Parkinson's disease
|September 23, 2023
概括
阿尔法同核素 (a-syn) 作为ER和线粒体之间的,调节吸收. 它的功能障碍,特别是129的酸化,损害了细胞从线粒体压力中恢复,可能导致帕金森病的发病.
科学领域:
- 细胞生物学 细胞生物学
- 神经科学是一个神经科学.
- 生物化学 生物化学
背景情况:
- 阿尔法同核素 (a-syn) 聚合与帕金森病 (PD) 有关,但其生理作用和参与PD病因学尚不清楚.
- 以前的研究表明,在压力下与线粒体膜的a-syn同位化.
研究的目的:
- 描述a-syn在调节内 (Ca2+) 流在内细胞网膜 (ER) 和线粒体之间的功能作用.
- 研究特定的a-syn域及其与线粒体相互作用中的翻译后修饰的参与及其在PD中的病理作用.
主要方法:
- 在RBL,HEK293和N2a细胞中A-syn的细胞表达.
- 测量线粒体Ca2+吸收的情况.
- 结构化照明显微镜用于评估ER-线粒体接触.
- 用与PD相关的毒素 (MPTP/MPP+,CCCP) 进行治疗,并评估a-syn酸化 (pS129) 和聚合.
主要成果:
- A-syn表达增强了ER介导的线粒体Ca2+吸收,这取决于N端螺旋.
- A-syn增加了ER和线粒体之间的接触.
- 在毒素引起的压力后,A-syn抑制了线粒体Ca2+吸收的恢复,涉及C-终端尾部和-129酸化.
- 暴露于毒素会诱导a-syn酸化 (pS129) 和聚合.
结论:
- A-syn 作为一个结合蛋白,调节 ER-线粒体 Ca2+ 流量,具有潜在的生理学意义.
- 在PD中A-syn的病理作用可能包括防止细胞从毒素诱导的线粒体功能障碍中恢复,特别是通过PS129修饰.
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