血红素
线粒体
细胞色素c
细胞色素C1
细胞色素
生物能学
细胞色素b
血红素蛋白
电子传输链
生物物理学
化学
细胞色素c氧化酶
线粒体膜间隙
线粒体内膜
膜电位
呼吸链
辅酶Q-细胞色素c还原酶
线粒体呼吸链
生物化学
细胞生物学
细菌外膜
生物
线粒体DNA
酶
基因
大肠杆菌
作者
Nadezda A. Brazhe,Evelina I. Nikelshparg,А. А. Байжуманов,Vera G. Grivennikova,Anna A. Semenova,Sergey M. Novikov,Valentyn S. Volkov,Aleksey V. Arsenin,Dmitry I. Yakubovsky,Andrey B. Evlyukhin,Zhanna V. Bochkova,Eugene A. Goodilin,Г. В. Максимов,Olga Sosnovtseva,Andrey B. Rubin
标识
DOI:10.1016/j.freeradbiomed.2023.01.013
摘要
The balance between the mitochondrial respiratory chain activity and the cell's needs in ATP ensures optimal cellular function. Cytochrome c is an essential component of the electron transport chain (ETC), which regulates ETC activity, oxygen consumption, ATP synthesis and can initiate apoptosis. The impact of conformational changes in cytochrome c on its function is not understood for the lack of access to these changes in intact mitochondria. We have developed a novel sensor that uses unique properties of label-free surface-enhanced Raman spectroscopy (SERS) to identify conformational changes in heme of cytochrome c and to elucidate their role in functioning mitochondria. We have verified that molecule bond vibrations assessed by SERS are a reliable indicator of the heme conformation during changes in the inner mitochondrial membrane potential and ETC activity. We have demonstrated that cytochrome c heme reversibly switches between planar and ruffled conformations in response to the inner mitochondrial membrane potential (ΔΨ) and H+ concentration in the intermembrane space. This regulates the efficiency of the mitochondrial respiratory chain, thus, adjusting the mitochondrial respiration to the cell's consumption of ATP and the overall activity. We have found that under hypertensive conditions cytochrome c heme loses its sensitivity to ΔΨ that can affect the regulation of ETC activity. The ability of the proposed SERS-based sensor to track mitochondrial function opens broad perspectives in cell bioenergetics.
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