线粒体脱极化稳定了细胞质中的维生素B12伴侣MMADHC,以增加MTR活动
Sneha P Rath1,2,3, Zhu Li4, Arkajit Guha4
1Department of Molecular Biology, Mass General Hospital, Boston, MA 02114, USA.
bioRxiv : the preprint server for biology
|January 9, 2026
概括
线粒体功能障碍引发了一种反应,其中维生素B12陪伴者MMADHC稳定并移动到细胞质中. 这会稳定 metionin 合成酶 (MTR),影响单碳代谢.
科学领域:
- 细胞生物学 细胞生物学
- 线粒体生物学 线粒体生物学
- 代谢过程中的代谢.
背景情况:
- 众所周知,PINK1和ATFS-1等线粒体蛋白质对质子动力 (PMF) 崩作出反应.
- 在PMF崩时蛋白质水平发生变化的系统识别对于理解细胞应激反应至关重要.
研究的目的:
- 为了识别那些在线粒体质子动力 (PMF) 崩后仅在蛋白质水平上增加的基因.
- 调查维生素B12伴侣MMADHC对PMF崩的反应及其对细胞代谢的影响.
主要方法:
- 联合蛋白质和RNA测序屏幕用于识别PMF崩后蛋白质水平的变化.
- 在mtDNA消耗增加期间,对MMADHC稳定和局部化的时间过程分析.
- 调查MMADHC对氨酸合成酶 (MTR) 活性的影响.
主要成果:
- 一个屏幕确定了10个候选基因,包括MMADHC和MTR,在PMF崩时在蛋白质水平上增加.
- 通常短暂的MMADHC在PMF崩期间稳定并积聚在细胞质中,而不是线粒体中,在PINK1激活之前.
- 稳定细胞质MMADHC可提高B12依赖酶MTR的水平和活性.
结论:
- 线粒体PMF通过MMADHC稳定性和细分来调节细胞质B12依赖的MTR.
- MMADHC充当PMF崩的传感器,通过MTR影响单碳代谢.
- 这项研究揭示了一种新的调节途径,将线粒体健康与细胞质代谢过程联系起来.
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