Riboul Danielle V, Crill Sarah, Oliva Carlos D, Restifo Maria G, Joseph Reggie, Joseph Kerdes, Nguyen Ken Cq, Hall David H, Fily Yaouen, Macleod Gregory T
bioRxiv. 2024 Mar 2:2023.05.30.542959. doi: 10.1101/2023.05.30.542959.
Neurons rely on mitochondria for an efficient supply of ATP and other metabolites. However, while neurons are highly elongated, mitochondria are discrete and limited in number. Due to the slow rates of diffusion over long distances it follows that neurons would benefit from an ability to control the distribution of mitochondria to sites of high metabolic activity, such as synapses. It is assumed that neurons' possess this capacity, but ultrastructural data over substantial portions of a neuron's extent that would allow for tests of such hypotheses are scarce. Here, we mined the Caenorhabditis elegans electron micrographs of John White and Sydney Brenner and found systematic differences in average mitochondrial length (ranging from 1.3 to 2.4 μm), volume density (3.7% to 6.5%) and diameter (0.18 to 0.24 μm) between neurons of different neurotransmitter type and function, but found limited differences in mitochondrial morphometrics between axons and dendrites of the same neurons. Analyses of distance intervals found mitochondria to be distributed randomly with respect to presynaptic specializations, and an indication that mitochondria were displaced from postsynaptic specializations. Presynaptic specializations were primarily localized to varicosities, but mitochondria were no more likely to be found in synaptic varicosities than non-synaptic varicosities. Consistently, mitochondrial volume density was no greater in varicosities with synapses. Therefore, beyond the capacity to disperse mitochondria throughout their length, at least in C. elegans, fine caliber neurons manifest limited sub-cellular control of mitochondrial size and distribution.
神经元依赖线粒体来高效供应三磷酸腺苷(ATP)和其他代谢产物。然而,尽管神经元高度细长,但线粒体是离散的且数量有限。由于长距离扩散速度缓慢,因此神经元若能将线粒体分布控制到高代谢活性部位(如突触)将受益匪浅。据推测,神经元具备这种能力,但能对这类假说进行检验的、覆盖神经元大部分范围的超微结构数据却很稀少。在此,我们挖掘了约翰·怀特(John White)和悉尼·布伦纳(Sydney Brenner)提供的秀丽隐杆线虫电子显微照片,发现不同神经递质类型和功能的神经元之间,线粒体的平均长度(范围为1.3至2.4μm)、体积密度(3.7%至6.5%)和直径(0.18至0.24μm)存在系统性差异,但同一神经元的轴突和树突之间线粒体形态计量学的差异有限。对距离间隔的分析发现,线粒体相对于突触前特化结构呈随机分布,且有迹象表明线粒体从突触后特化结构处移位。突触前特化结构主要定位于膨体,但线粒体在突触膨体中出现的可能性并不比非突触膨体更高。同样,有突触的膨体中线粒体体积密度也没有更大。因此,至少在秀丽隐杆线虫中,除了能在线粒体全长范围内进行分散外,细径神经元对线粒体大小和分布的亚细胞控制有限。