肝脏的棕基蛋白质和基蛋白化酶蛋白亲近性网络连接了脂质修饰和线粒体
Sarah L Speck1, Dhaval P Bhatt2, Qiang Zhang1
1Division of Endocrinology, Metabolism & Lipid Research, Washington University, St. Louis, MO 63110, USA.
Cell reports
|November 5, 2023
概括
乙-蛋白质二聚酶1和2 (APT1和APT2) 通过去除线粒体蛋白质来调节葡萄糖代谢. 这些酶在肝脏中的双删除会导致胰岛素抵抗和高血糖症,这表明在代谢调节中存在功能冗余.
科学领域:
- 生物化学 生物化学
- 代谢调节 代谢调节 代谢调节
- 线粒体功能的功能
背景情况:
- 乙蛋白类化酶1和2 (APT1和APT2) 逆转S-乙化,这是一种影响全身葡萄糖代谢的过程.
- 线粒体蛋白对于细胞能量生产和代谢控制至关重要.
研究的目的:
- 研究APT1和APT2在肝脏葡萄糖代谢和胰岛素信号传递中的作用.
- 为了识别APT1和APT2基质和蛋白相互作用网络.
主要方法:
- 在肝脏特异性淘汰赛小鼠中的棕化蛋白质组学.
- 在HepG2细胞中基于miniTurbo的蛋白质-蛋白质近距离网络分析.
- 在高脂肪饮食养的小鼠中评估代谢参数,并进行向基因删除.
主要成果:
- APT1主要去除线粒体蛋白质,包括那些参与谷氨酸代谢的蛋白质.
- APT1和APT2与线粒体转位酶 (Tomm20,Timm44) 和谷氨酸运输体Slc1a5 (ASCT2) 形成接近网络.
- 在小鼠中,APT1和APT2的双重肝除导致胰岛素耐药性,高血糖症,葡萄糖生成增加和肝脏质量减少.
结论:
- APT1和APT2在调节肝脏葡萄糖代谢和胰岛素信号传递方面表现出功能冗余.
- 这些酶对于维持代谢平衡至关重要,它们的失调有助于代谢疾病.
- 已识别的基板和网络为了解APT1/APT2在代谢健康和疾病中的功能提供了一个框架.
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