Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA.
Division of Cardiology, Department of Internal Medicine, Loyola University Medical Center, Maywood, Illinois, USA.
Neuroendocrinology. 2022;112(4):324-337. doi: 10.1159/000517273. Epub 2021 May 25.
Mitochondria are essential organelles required for several cellular processes ranging from ATP production to cell maintenance. To provide energy, mitochondria are transported to specific cellular areas in need. Mitochondria also need to be recycled. These mechanisms rely heavily on trafficking events. While mechanisms are still unclear, hypothalamic mitochondria are linked to obesity.
We used C2 domain protein 5 (C2CD5, also called C2 domain-containing phosphoprotein [CDP138]) whole-body KO mice primary neuronal cultures and cell lines to perform electron microscopy, live cellular imaging, and oxygen consumption assay to better characterize mitochondrial alteration linked to C2CD5.
This study identified that C2CD5 is necessary for proper mitochondrial trafficking, structure, and function in the hypothalamic neurons. We previously reported that mice lacking C2CD5 were obese and displayed reduced functional G-coupled receptor, melanocortin receptor 4 (MC4R) at the surface of hypothalamic neurons. Our data suggest that in neurons, normal MC4R endocytosis/trafficking necessities functional mitochondria.
Our data show that C2CD5 is a new protein necessary for normal mitochondrial function in the hypothalamus. Its loss alters mitochondrial ultrastructure, localization, and activity within the hypothalamic neurons. C2CD5 may represent a new protein linking hypothalamic dysfunction, mitochondria, and obesity.
线粒体是细胞内必需的细胞器，参与多种细胞过程，包括 ATP 生成和细胞维持。为了提供能量，线粒体被运输到特定的需要的细胞区域。线粒体也需要被回收。这些机制严重依赖于运输事件。虽然机制尚不清楚，但下丘脑的线粒体与肥胖有关。
我们使用 C2 结构域蛋白 5（C2CD5，也称为 C2 结构域包含磷酸蛋白[CDP138]）全身敲除小鼠原代神经元培养物和细胞系进行电子显微镜、活细胞成像和耗氧测定，以更好地表征与 C2CD5 相关的线粒体改变。
本研究确定 C2CD5 是下丘脑神经元中线粒体运输、结构和功能所必需的。我们之前报道过，缺乏 C2CD5 的小鼠肥胖，下丘脑神经元表面的功能性 G 蛋白偶联受体黑素皮质素受体 4（MC4R）减少。我们的数据表明，在神经元中，正常的 MC4R 内吞/运输需要功能性线粒体。
我们的数据表明，C2CD5 是下丘脑正常线粒体功能所必需的新蛋白。它的缺失改变了下丘脑神经元中线粒体的超微结构、定位和活性。C2CD5 可能代表一种新的蛋白，将下丘脑功能障碍、线粒体和肥胖联系起来。
