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.

中文翻译：

---

哺乳动物复合物I中缺血诱导的调节开关的分子机制


呼吸复合物 I 是哺乳动物线粒体氧化磷酸化的有效驱动因素，但其在挑战性条件下不受控制的催化会导致氧化应激和细胞损伤。缺血条件将复合物 I 从快速、可逆的催化作用转变为休眠状态，以在再氧合时提供保护，但这种转换的分子基础尚不清楚。我们将复合物 I 催化的精确生化定义与偶联囊泡磷脂双层中的高分辨率冷冻电子显微镜结构相结合，揭示了由膜相互作用调节的进入休眠状态的转变机制。通过实施多功能膜系统来统一结构和功能，将催化和调节特性归因于特定的结构状态，我们定义了复合物 I 中的构象开关如何控制其生理作用。