亚甲蓝不能绕过小鼠脑线粒体中复合物 III 抗霉素的阻断。
Methylene blue does not bypass Complex III antimycin block in mouse brain mitochondria.
机构信息
Department of Genetics, Cytology and Bioengineering, Voronezh State University, Russia.
Voronezh State University of Engineering Technology, Voronezh, Russia.
出版信息
FEBS Lett. 2019 Mar;593(5):499-503. doi: 10.1002/1873-3468.13332. Epub 2019 Feb 20.
Abstract
Methylene blue (MB) is a promising prodrug to treat mitochondrial dysfunctions that is currently being used in clinical trials for Alzheimer's disease. MB can penetrate the blood brain barrier, accumulating in brain mitochondria where it acts as a redox mediator in the electron transfer chain (ETC). Mitochondrial flavins are thought to reduce MB, which is then oxidized by cytochrome c, thereby bypassing inhibited Complex I of ETC. We found that in mouse brain mitochondria, MB fails to restore the membrane potential and respiration inhibited by antimycin. Furthermore, antimycin inhibits MB-induced H O generation. Our data suggest that the acceptor of electrons from MB is a Qo ubiquinol-binding site of Complex III; thus, MB-based drugs might not be helpful in mitochondrial dysfunctions involving Complex III inhibition.
摘要
亚甲蓝（MB）是一种有前途的治疗线粒体功能障碍的前药，目前正在阿尔茨海默病的临床试验中使用。MB 可以穿透血脑屏障，在脑线粒体中积累，在那里它作为电子传递链（ETC）中的氧化还原介质发挥作用。线粒体黄素被认为可以还原 MB，然后被细胞色素 c 氧化，从而绕过 ETC 中受抑制的复合物 I。我们发现，在小鼠脑线粒体中，MB 不能恢复由安密妥因抑制的膜电位和呼吸作用。此外，安密妥因抑制 MB 诱导的 H 2 O 2 生成。我们的数据表明，MB 电子的受体是复合物 III 的 Qo 泛醌结合位点；因此，基于 MB 的药物可能无助于涉及复合物 III 抑制的线粒体功能障碍。
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