Abstract：
The dynamicity of the mitochondrial network is crucial for meeting the ever-changing metabolic and energy needs of the cell. Mitochondrial fission promotes the degradation and distribution of mitochondria, while mitochondrial fusion maintains mitochondrial function through the complementation of mitochondrial components. Previously, we have reported that mitochondrial networks are tubular, interconnected, and well-organized in young, healthy C. elegans, but become fragmented and disorganized with advancing age and in models of age-associated neurodegenerative disease. In this work, we examine the effects of increasing mitochondrial fission or mitochondrial fusion capacity by ubiquitously overexpressing the mitochondrial fission gene drp-1 or the mitochondrial fusion genes fzo-1 and eat-3, individually or in combination. We then measured mitochondrial function, mitochondrial network morphology, physiologic rates, stress resistance, and lifespan. Surprisingly, we found that overexpression of either mitochondrial fission or fusion machinery both resulted in an increase in mitochondrial fragmentation. Similarly, both mitochondrial fission and mitochondrial fusion overexpression strains have extended lifespans and increased stress resistance, which in the case of the mitochondrial fusion overexpression strains appears to be at least partially due to the upregulation of multiple pathways of cellular resilience in these strains. Overall, our work demonstrates that increasing the expression of mitochondrial fission or fusion genes extends lifespan and improves biological resilience without promoting the maintenance of a youthful mitochondrial network morphology. This work highlights the importance of the mitochondria for both resilience and longevity.
摘要：
线粒体网络的动态性对于满足细胞不断变化的代谢和能量需求至关重要。线粒体裂变促进线粒体的降解和分布，而线粒体融合通过线粒体成分的互补维持线粒体功能。以前,我们已经报道了线粒体网络是管状的，互联,年轻时组织良好，健康的秀丽隐杆线虫,但随着年龄的增长和与年龄相关的神经退行性疾病的模型变得支离破碎和混乱。在这项工作中,我们研究了通过普遍过表达线粒体裂变基因drp-1或线粒体融合基因fzo-1和eat-3，单独或联合表达增加线粒体裂变或线粒体融合能力的影响。然后我们测量了线粒体功能，线粒体网络形态学，生理率，抗应力，和寿命。令人惊讶的是,我们发现线粒体分裂或融合机制的过表达均导致线粒体片段化增加.同样，线粒体分裂和线粒体融合过表达菌株都延长了寿命和增加了抗逆性，在线粒体融合过表达菌株的情况下，这似乎至少部分是由于这些菌株中多种细胞弹性途径的上调。总的来说,我们的工作表明，增加线粒体裂变或融合基因的表达可以延长寿命，并改善生物恢复能力，而不会促进年轻线粒体网络形态的维持。这项工作强调了线粒体对复原力和长寿的重要性。
