复合体I内的还氧化枢纽的氨酸氧化可以促进电子运输链超复合体的形成
Runtai Chen1, Seyed Amirhossein Tabatabaei Dakhili2, Rokas Gerulskis3
1Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; Cardiovascular Research Institute, University of Alberta, Edmonton, Alberta, Canada; Cancer Research Institute of Northern Alberta, University of Alberta, Edmonton, Alberta, Canada.
线粒体电子运输链通过形成超级复合体,适应过多的活性氧物种,增强能量生产和治疗癌症的潜力.
科学领域:
- 线粒体生物学 线粒体生物学
- 细胞呼吸 细胞呼吸
- 氧化还原信号传递.
背景情况:
- 线粒体电子运输链 (ETC) 为ATP合成产生线粒体膜潜力 (ΔΨm),并产生线粒体反应性氧物种 (mtROS).
- 通过ETC感知并适应过度的mtROS以维持ΔΨm的机制尚未完全理解.
研究的目的:
- 研究ETC如何感知过度的mtROS,并适应增强ΔΨm.
- 确定参与ETC适应mtROS的分子参与者.
主要方法:
- 在复合体I的Ndufs1中确定一个氧化还原枢纽 (Cys残留64,75,78,92).
- 呼吸体超复杂的形成和复杂I活动的分析.
- 使用氧化模拟剂 (C92D) Ndufs1-knockin A549细胞和生物电池平台.
- 评估了诱导mtROS的化疗药物的治疗疗效.
主要成果:
- 氧化Ndufs1 Cys残留物促进了复合体I的合并到呼吸体超级复合体中.
- 这种氧化会损害复合I活性,而复合I活性则通过超复合集成来挽救.
- Ndufs1-knockin细胞表现出更高的ETC超复杂水平,ΔΨm和氧气消耗.
- 破坏ETC超级复杂物增强了癌细胞中的化疗疗效.
结论:
- 在Ndufs1中的还氧化枢纽调节ETC超复合体的形成,以响应mtROS.
- 超复杂的ETC转化是维持线粒体功能的一个关键适应机制.
- 准ETC超级复杂物可能通过增加对mtROS诱导剂的敏感性来增强癌症治疗.
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