酸盐是哺乳动物电子传输链中的终端电子受体
Jessica B Spinelli1,2, Paul C Rosen1,2,3, Hans-Georg Sprenger1,2
1Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Science (New York, N.Y.)
|December 2, 2021
概括
当氧气有限时,哺乳动物可以使用烟酸作为替代电子受体,从而使线粒体电子运输链 (ETC) 保持功能. 在低氧状态下,这种逆转功能维持了细胞呼吸.
科学领域:
- 生物化学
- 细胞呼吸
- 线粒体功能
背景情况:
- 线粒体电子运输链 (ETC) 通常使用氧气作为终端电子受体 (TEA).
- 细胞呼吸和ATP产生严重依赖于通过ETC的连续电子流.
- 减少氧气的阻碍对维护线粒体功能构成重大挑战.
研究的目的:
- 在氧降低受阻时,研究线粒体ETC中电子流的替代途径.
- 在哺乳动物细胞中识别替代终端电子受体.
- 了解在低氧条件下维持线粒体功能的机制.
主要方法:
- 在细胞模型中抑制氧气减少.
- 在ETC中测量电子流量和代谢物水平.
- 酶活性分析,包括糖酸脱酶 (SDH) 复合物.
- 在各种小鼠组织中评估富马酸作为TEA的作用.
主要成果:
- 复合I和二酸脱酶 (DHODH) 即使阻断了氧降解,也可以将电子沉积到ETC中.
- 在受抑制的氧降解下,ubiquinol的积累会导致SDH复合体逆转.
- 这种反向的SDH活动使得电子沉积到烟酸上,维持DHODH和复合物I.
- 鼠标组织表现出各种能力,以利用烟酸作为TEA,通常在缺氧下逆转SDH活动.
结论:
- 哺乳动物细胞在ETC中拥有一个电子流的电路,当氧气有限时,该电路将烟酸作为TEA.
- SDH复合体的反向功能是维持在缺氧条件下的线粒体功能的一个关键机制.
- 这种替代的电子流通途径突显了细胞呼吸对低氧环境的适应性.
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