Lange Felix, Ratz Michael, Dohrke Jan-Niklas, Le Vasseur Maxence, Wenzel Dirk, Ilgen Peter, Riedel Dietmar, Jakobs Stefan
Department of NanoBiophotonics, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Clinic of Neurology, University Medical Center Göttingen, Göttingen, Germany.
Nat Cell Biol. 2025 Apr;27(4):633-640. doi: 10.1038/s41556-025-01620-1. Epub 2025 Mar 21.
Prohibitins are a highly conserved family of proteins that have been implicated in a variety of functions including mitochondrial stress signalling and housekeeping, cell cycle progression, apoptosis, lifespan regulation and many others. The human prohibitins prohibitin 1 and prohibitin 2 have been proposed to act as scaffolds within the mitochondrial inner membrane, but their molecular organization has remained elusive. Here we determined the molecular organization of the human prohibitin complex within the mitochondrial inner membrane using an integrative structural biology approach combining quantitative western blotting, cryo-electron tomography, subtomogram averaging and molecular modelling. The proposed bell-shaped structure consists of 11 alternating prohibitin 1 and prohibitin 2 molecules. This study reveals an average of about 43 prohibitin complexes per crista, covering 1-3% of the crista membrane area. These findings provide a structural basis for understanding the functional contributions of prohibitins to the integrity and spatial organization of the mitochondrial inner membrane.
prohibitin蛋白是一个高度保守的蛋白质家族，涉及多种功能，包括线粒体应激信号传导和日常维护、细胞周期进程、细胞凋亡、寿命调节等诸多方面。人类的prohibitin蛋白，即prohibitin 1和prohibitin 2，被认为在线粒体内膜中充当支架，但它们的分子组织仍然难以捉摸。在这里，我们使用了一种综合结构生物学方法，结合定量蛋白质免疫印迹、冷冻电子断层扫描、亚断层平均和分子建模，确定了线粒体内膜中人类prohibitin复合物的分子组织。所提出的钟形结构由11个交替的prohibitin 1和prohibitin 2分子组成。这项研究揭示，每个嵴平均约有43个prohibitin复合物，覆盖嵴膜面积的1 - 3%。这些发现为理解prohibitin蛋白对线粒体内膜完整性和空间组织的功能贡献提供了结构基础。
