线粒体呼吸链复合物Ⅰ结构和功能的研究进展

摘要

Mitochondrial respiratory chain complex Ⅰ is located in the mitochondrial inner membrane,and it's also one of the most important protein complexes in the respiratory chain.Electrons can be transferred from NADH to CoQ through complex Ⅰ while coupling four protons from the mitochondrial matrix to the membrane gap to form a transmembrane proton gradient that drives ATP synthesis.In the present study,the crystal structure of complex Ⅰ has been clear,including 14 central subunits,which constitute the peripheral domain and the membrane domain,respectively.The peripheral domain is responsible for the transfer of electrons.The membrane domain is responsible for the proton Pump out.Since there are multiple intermediate states in the electron transport process,complex Ⅰ is the main site of reactive oxygen species in the organism.The complex Ⅰ can also be converted by the A/D state to reduce the generation of reactive oxygen species.It is currently speculated that the electrostatic action produced by electron transport in complex Ⅰ can change its structure to drive proton pumping,but its specific mechanism remains unclear.The defects of complex Ⅰ function are a variety of neurodegenerative diseases,including Alzheimer's disease,Parkinson's,etc.,mainly due to the mutation of the different subunits.This paper reviews the progress of the structure and function of complex Ⅰ and prospects for future research.%线粒体呼吸链复合物Ⅰ位于线粒体的内膜,是呼吸链中最重要的蛋白复合体之一,可以将电子从NADH传递至CoQ,同时偶联四个质子从线粒体基质泵出至膜间隙,形成跨膜质子梯度,驱动ATP的合成.在目前的研究中,关于复合物Ⅰ的晶体结构已经比较清楚,包括14个中心亚基,分别构成外周结构域和膜结构域,其中外周结构域负责电子的传递,膜结构域负责质子的泵出.由于在电子传递过程中存在多个中间态阶段,因此复合物Ⅰ是机体中活性氧产生的主要位点.复合物Ⅰ也可以通过A/D状态之间的转换,降低活性氧的产生.学者认为复合物Ⅰ中电子传递产生的静电作用可以改变其结构,从而驱动质子的泵出,但是其具体机制仍不明确.复合物Ⅰ功能的缺陷是多种神经退行性疾病的诱因,包括阿兹海默症、帕金森等,主要是由于其中不同亚基的点突变导致.本文综述了复合物Ⅰ结构和功能的研究进展,并对今后的研究做出展望.