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通过与BNIP3和NIX的近接和动态相互作用,PPTC7限制了线粒

Lianjie Wei¹, Mehmet Oguz Gok², Jordyn D Svoboda¹

¹Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine in St. Louis, St. Louis, MO, 63110, USA.

bioRxiv : the preprint server for biology

|February 8, 2024

概括

蛋白酸酶7 (PPTC7) 通过促进BNIP3和NIX蛋白质的降解来调节甲基. PPTC7的损失增加了这些线粒体受体,而其在外层线粒体膜上的存在则促进了它们的周转.

科学领域:

线粒体生物学线粒体生物学
细胞平衡是细胞的平衡.
蛋白质降解途径蛋白质降解途径

背景情况:

蛋白酸酶7 (PPTC7) 是一种线粒体酶,对于维持代谢平衡至关重要.
以前的研究将PPTC7淘汰与线粒的增加联系在一起,但确切的机制尚不清楚.
受体介导的线粒,涉及诸如BNIP3和NIX之类的蛋白质,对于线粒体质量控制至关重要.

研究的目的:

阐明PPTC7在调节受体介导线粒细胞衰变中的作用.
研究PPTC7影响BNIP3和NIX蛋白水平的分子机制.
为了确定PPTC7参与线粒调节的亚细胞局部化和相互作用.

主要方法:

在PPTC7淘汰赛和过度表达模型中对BNIP3和NIX表达的后转录分析.
使用蛋白质酶抑制试验评估蛋白质半衰期和循环.
亚细胞局部化研究,包括外线粒体膜定,以及近距离标记以确定蛋白质相互作用.

主要成果:

PPTC7的损失导致BNIP3和NIX的转录后上调,独立于HIF-1α.
PPTC7促进了BNIP3和NIX的普基因介导循环,延长了PPTC7缺乏细胞中的半衰期.
PPTC7的一小部分局限于外层线粒体膜,在那里它与BNIP3和NIX直接结合,以促进它们的蛋白质体降解.

结论:

PPTC7通过促进BNIP3和NIX的降解,作为线粒细胞衰变的负调节剂.
需要PPTC7的催化活性,但其线粒体矩阵局部化不需要这个功能.
对PPTC7在线粒体外膜的动态招募是控制线粒体受体周转的关键机制.

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