<br>线粒体裂变或线粒体融合基因的过表达可增强恢复力并延长寿命,Aging Cell

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线粒体裂变或线粒体融合基因的过表达可增强恢复力并延长寿命
Aging Cell ( IF 8.0 ) Pub Date : 2024-07-02 , DOI: 10.1111/acel.14262
Annika Traa _{1,

2,

3} , Allison Keil _{1,

2,

3} , Abdelrahman AlOkda _{1,

2,

3} , Suleima Jacob-Tomas _{1,

2,

3} , Aura A Tamez González _{1,

2,

3} , Shusen Zhu _{1,

2,

3} , Zenith Rudich _{1,

2,

3} , Jeremy M Van Raamsdonk _{1,

2,

3,

4}

Affiliation

线粒体网络的动力学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来维持线粒体功能。以前，我们已经报道过，线粒体网络在年轻、健康的秀丽隐杆线虫中是管状的、相互连接的和组织良好的，但随着年龄的增长和年龄相关的神经退行性疾病的模型，线粒体网络变得碎片化和杂乱无章。在这项工作中，我们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 单独或组合来研究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、生理速率、抗逆性和寿命。令人惊讶的是，我们发现线粒体裂变或融合机制的过表达都导致线粒体碎裂的增加。同样，线粒体裂变和线粒体融合过表达菌株都延长了寿命并增加了抗逆性，就线粒体融合过表达菌株而言，这似乎至少部分是由于这些菌株中细胞弹性的多种途径的上调。总体而言，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提高生物恢复力，而不会促进维持年轻的线粒体网络形态。这项工作强调了线粒体对弹性和寿命的重要性。

"点击查看英文标题和摘要"

Overexpression of mitochondrial fission or mitochondrial fusion genes enhances resilience and extends longevity

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.

更新日期：2024-07-02

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