Mitochondrial network reorganization and transient expansion during oligodendrocyte generation.
Mitochondrial network reorganization and transient expansion during oligodendrocyte generation.
复制标题
少突胶质细胞生成过程中线粒体网络重组和短暂扩张。
DOI：
10.1101/2023.12.05.570104
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Hill,RobertA
中科院分区：
文献类型：
--
作者：
Bame,Xhoela;Hill,RobertA
少突胶质细胞前体细胞（OPCs）产生脑的髓鞘化少突胶质细胞。这一过程持续一生，对于神经退行性疾病的恢复至关重要。为了更好地了解少突胶质细胞发生过程中的细胞检查点，我们确定了小鼠和人类大脑皮层中少突胶质细胞谱系的线粒体分布和形态计量学。在少突胶质细胞生成过程中，线粒体内容物的扩展同时与亚细胞分区向远端进程的变化。这些变化之后，少突胶质细胞过程中的线粒体和髓鞘突然丢失，与鞘致密化一致。这种重组和广泛的扩展和消耗需要3天。少突胶质细胞线粒体在数天内是静止的，而OPC线粒体运动在数分钟内由动物唤醒状态调节。老年OPCs还显示线粒体大小、体积分数和运动性降低。因此，线粒体动力学与少突胶质细胞的产生有关，通过其局部微环境动态地改变，并在衰老的大脑中改变。
Oligodendrocyte precursor cells (OPCs) give rise to myelinating oligodendrocytes of the brain. This process persists throughout life and is essential for recovery from neurodegeneration. To better understand the cellular checkpoints that occur during oligodendrogenesis, we determined the mitochondrial distribution and morphometrics across the oligodendrocyte lineage in mouse and human cerebral cortex. During oligodendrocyte generation, mitochondrial content expands concurrently with a change in subcellular partitioning towards the distal processes. These changes are followed by an abrupt loss of mitochondria in the oligodendrocyte processes and myelin, coinciding with sheath compaction. This reorganization and extensive expansion and depletion take 3 days. Oligodendrocyte mitochondria are stationary over days while OPC mitochondrial motility is modulated by animal arousal state within minutes. Aged OPCs also display decreased mitochondrial size, volume fraction, and motility. Thus, mitochondrial dynamics are linked to oligodendrocyte generation, dynamically modified by their local microenvironment, and altered in the aging brain.