人类硫化基氧降解酶的硫化物依赖激活
Joseph V Roman1, Yashvi Shukla1, David A Hanna1
1Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109.
The Journal of biological chemistry
|September 5, 2025
概括
硫化 (H2S) 暴露通过转化后机制激活线粒体硫化氧降解酶 (SQOR). 这项研究揭示了H2S如何调节SQOR活动,影响细胞呼吸和排毒.
科学领域:
- 生物化学
- 细胞代谢
- 酶调节
背景情况:
- 硫化 (H2S) 是一种有毒气体和代谢副产品.
- 线粒体硫化氧降解酶 (SQOR) 通过氧化和降低辅酶Q来排毒H2S.
- SQOR具有独特的囊三硫化辅因子,与其他黄二硫化还原酶不同.
研究的目的:
- 研究由H2S激活SQOR的机制.
- 确定H2S暴露是否影响SQOR活动.
- 阐明翻译后修改在SQOR法规中的作用.
主要方法:
- 将人类结肠腺癌 (HT-29) 和内皮细胞 (EA.hy926) 暴露在H2S中.
- 测量SQOR活动和蛋白质水平.
- 使用CRISPR对硫转移酶 (MPST,TST) 的淘汰.
- 使用药物抑制和囊补充剂.
主要成果:
- 在HT-29细胞中,H2S暴露增加了SQOR活性5倍,在EA.hy926细胞中增加了2倍.
- 增加的SQOR活性与较高的蛋白质水平无关,这表明后翻译调节.
- 在CRISPR中,硫转移酶被排除在SQOR激活之外.
- H2S,而不是低分子量硫化物,调节SQOR活动.
结论:
- 通过H2S激活SQOR涉及一个后翻译机制.
- 通过囊氧化和硫化物添加的三硫化物安装和激活的模型被提出.
- H2S在需要时自主调节SQOR活动,表明细胞有保护性反应.
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