Institute of Clinical Neurobiology, University Hospital Wuerzburg, Wuerzburg, Germany.
Institute of Clinical Neurobiology, University Hospital Wuerzburg, Wuerzburg, Germany.
Neurobiol Dis. 2024 Apr;193:106454. doi: 10.1016/j.nbd.2024.106454. Epub 2024 Feb 24.
Axonal mitochondria defects are early events in the pathogenesis of motoneuron disorders such as spinal muscular atrophy and amyotrophic lateral sclerosis. The RNA-binding protein hnRNP R interacts with different motoneuron disease-related proteins such as SMN and TDP-43 and has important roles in axons of motoneurons, including axonal mRNA transport. However, whether hnRNP R also modulates axonal mitochondria is currently unknown. Here, we show that axonal mitochondria exhibit altered function and motility in hnRNP R-deficient motoneurons. Motoneurons lacking hnRNP R show decreased anterograde and increased retrograde transport of mitochondria in axons. Furthermore, hnRNP R-deficiency leads to mitochondrial hyperpolarization, caused by decreased complex I and reversed complex V activity within the respiratory chain. Taken together, our data indicate a role for hnRNP R in regulating transport and maintaining functionality of axonal mitochondria in motoneurons.
轴突线粒体缺陷是运动神经元疾病（如脊髓性肌萎缩症和肌萎缩侧索硬化症）发病机制中的早期事件。RNA 结合蛋白 hnRNP R 与不同的运动神经元疾病相关蛋白（如 SMN 和 TDP-43）相互作用，在运动神经元的轴突中具有重要作用，包括轴突 mRNA 运输。然而，hnRNP R 是否也调节轴突线粒体目前尚不清楚。在这里，我们表明 hnRNP R 缺陷型运动神经元中的轴突线粒体表现出功能和运动异常。缺乏 hnRNP R 的运动神经元显示出线粒体在轴突中的顺行和逆行运输减少。此外，hnRNP R 缺陷导致线粒体超极化，这是由呼吸链中复合物 I 减少和复合物 V 活性逆转引起的。总之，我们的数据表明 hnRNP R 在调节运动神经元中轴突线粒体的运输和维持其功能方面发挥作用。
