研究人员表示，呼吸复合体I是哺乳动物线粒体中氧化磷酸化的有效驱动力，但它在挑战性条件下的失控催化会导致氧化应激和细胞损伤。缺血条件会将复合体I从快速、可逆的催化转换为休眠状态，从而在复氧后起到保护作用，但这种转换的分子基础尚不清楚。
研究人员将复合体I催化的精确生化定义与耦合囊泡磷脂双分子层中的高分辨率冷冻电镜结构相结合，揭示了受膜相互作用调节的休眠状态转换机制。通过采用多功能膜系统将结构和功能结合起来，将催化和调节特性归因于特定的结构状态，研究人员确定了复合体I的构象转换如何控制其生理作用。
附：英文原文
Title: Molecular mechanism of the ischemia-induced regulatory switch in mammalian complex I
Author: Daniel N. Grba, John J. Wright, Zhan Yin, William Fisher, Judy Hirst
Issue&Volume: 2024-06-14
Abstract: Respiratory complex I is an efficient driver for oxidative phosphorylation in mammalian mitochondria, but its uncontrolled catalysis under challenging conditions leads to oxidative stress and cellular damage. Ischemic conditions switch complex I from rapid, reversible catalysis into a dormant state that protects upon reoxygenation, but the molecular basis for the switch is unknown. We combined precise biochemical definition of complex I catalysis with high-resolution cryo–electron microscopy structures in the phospholipid bilayer of coupled vesicles to reveal the mechanism of the transition into the dormant state, modulated by membrane interactions. By implementing a versatile membrane system to unite structure and function, attributing catalytic and regulatory properties to specific structural states, we define how a conformational switch in complex I controls its physiological roles.
DOI: ado2075
Source: https://www.science.org/doi/10.1126/science.ado2075