Joseph Ivor, Han Jiangmeng, Bianchi-Smak Jared, Yang Jiaxing, Bhupana Jagannatham Naidu, Flores Juan, Delucia Jack, Tran Tracy S, Goldenring James R, Bonder Edward M, Gao Nan
Department of Biological Sciences, Rutgers University, Newark, NJ, United States.
Department of Pharmacology, Physiology, and Neuroscience, Rutgers New Jersey Medical School, Newark, NJ, United States.
Front Cell Dev Biol. 2025 Apr 3;13:1498902. doi: 10.3389/fcell.2025.1498902. eCollection 2025.
The RAB11 family of small GTPases are intracellular regulators of membrane and vesicular trafficking. We recently reported that RAB11A and RAB11B redundantly regulate spindle dynamics in dividing gut epithelial cells. However, in contrast to the well-studied RAB11A functions in transporting proteins and lipids through recycling endosomes, the distinct function of RAB11B is less clear.
Our proteomic analysis of RAB11A or RAB11B interactome suggested a potential RAB11B specific involvement in regulating mitochondrial functions. Transcriptomic analysis of Rab11b knockout mouse intestines revealed an enhanced mitochondrial protein targeting program with an altered mitochondrial functional integrity. Flow cytometry assessment of mitochondrial membrane potential and reactive oxygen species production revealed an impaired mitochondrial function in vivo. Electron microscopic analysis demonstrated a particularly severe mitochondrial membrane defect in Paneth cells.
These genetic and functional data link RAB11B to mitochondrial structural and functional maintenance for the first time.
小GTP酶的RAB11家族是膜和囊泡运输的细胞内调节因子。我们最近报道，RAB11A和RAB11B在调节肠道上皮细胞分裂中的纺锤体动力学方面存在冗余作用。然而，与RAB11A通过再循环内体运输蛋白质和脂质的功能已得到充分研究不同，RAB11B的独特功能尚不清楚。
我们对RAB11A或RAB11B相互作用组的蛋白质组学分析表明，RAB11B可能特异性参与调节线粒体功能。对Rab11b基因敲除小鼠肠道的转录组分析显示，线粒体蛋白靶向程序增强，线粒体功能完整性改变。流式细胞术评估线粒体膜电位和活性氧产生，揭示了体内线粒体功能受损。电子显微镜分析表明，潘氏细胞中的线粒体膜缺陷尤为严重。
这些遗传和功能数据首次将RAB11B与线粒体结构和功能维持联系起来。
