酸盐脱酶在巨细胞代谢重编程过程中作为分子内氧基发生器起作用
Erika M Palmieri1, Ronald Holewinski2, Christopher L McGinity1
1Cancer Innovation Laboratory, NCI-Frederick, Frederick, MD, 21702, USA.
Nature communications
|August 22, 2023
概括
氧化 (NO) 通过产生氧化 (HNO) 来重新编程巨细胞代谢,从而不可逆转地改变酸盐脱酶复合体. 这种HNO生产对于M1巨细胞中NO依赖的代谢重新连接至关重要.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 由于氧化 (NO) 重编程线粒体新陈代谢,M1巨细胞采用了糖溶性状态.
- NO限制了akonitase 2和pyruvate dehydrogenase (PDH) 的活性,影响了巨细胞的代谢途径.
研究的目的:
- 调查NO向PDH复合体的机制.
- 为了确定酸盐在NO介导的代谢重编程中的作用.
- 阐明氧化 (HNO) 的生理生产和功能.
主要方法:
- 在NO丰富的巨细胞中对PDH复合物修饰的分析.
- 生物化学测试以评估二利胺脱酶 (DLD) 活性.
- 质谱测量用于识别蛋白质修饰.
- 分子建模和位点定向突变发生,以研究DLD功能.
主要成果:
- NO通过使用脂酸盐产生氧化物 (HNO) 来向PDH复合体.
- 酸被修改,而DLD酶在NO丰富的巨细胞中被不可逆转地抑制.
- HNO对蛋白质硫醇 (包括硫胺) 形成不可逆转的修饰,并在Cys477和Cys484中损害DLD同位体的形成.
- 在巨细胞中发现了抗减少蛋白质修饰的特征.
结论:
- 在生理上产生HNO,其产生依赖于富含酸盐的PDH复合物.
- 通过HNO介导的不可逆转修饰对于M1巨细胞中NO依赖的代谢重新连接至关重要.
- 这项研究揭示了免疫细胞代谢调节的新机制.
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