Euglena gracilis, a model organism of the eukaryotic supergroup Discoba harbouring also clinically important parasitic species, possesses diverse metabolic strategies and an atypical electron transport chain. While structures of the electron transport chain complexes and supercomplexes of most other eukaryotic clades have been reported, no similar structure is currently available for Discoba, limiting the understandings of its core metabolism and leaving a gap in the evolutionary tree of eukaryotic bioenergetics. Here, we report high-resolution cryo-EM structures of Euglena’s respirasome I + III₂ + IV and supercomplex III₂ + IV₂. A previously unreported fatty acid synthesis domain locates on the tip of complex I’s peripheral arm, providing a clear picture of its atypical subunit composition identified previously. Individual complexes are re-arranged in the respirasome to adapt to the non-uniform membrane curvature of the discoidal cristae. Furthermore, Euglena’s conformationally rigid complex I is deactivated by restricting ubiquinone’s access to its substrate tunnel. Our findings provide structural insights for therapeutic developments against euglenozoan parasite infections.

细小眼虫是真核超群 Discoba 的模式生物，也具有临床上重要的寄生物种，具有多种代谢策略和非典型电子传递链。虽然大多数其他真核生物分支的电子传递链复合物和超复合物的结构已被报道，但目前 Discoba 还没有类似的结构，这限制了对其核心代谢的理解，并在真核生物能量学的进化树中留下了空白。在这里，我们报告了眼虫呼吸体 I + III ₂ + IV 和超复合物 III ₂ + IV ₂的高分辨率冷冻电镜结构。先前未报道的脂肪酸合成结构域位于复合物 I 外周臂的尖端，提供了先前确定的其非典型亚基组成的清晰图像。各个复合物在呼吸体中重新排列，以适应盘状嵴的不均匀膜曲率。此外，眼虫的构象刚性复合物 I 通过限制泛醌进入其底物通道而失活。我们的研究结果为针对裸虫寄生虫感染的治疗开发提供了结构见解。