The Role of Respiratory Complex IV in Lifespan Length and Quality
The Role of Respiratory Complex IV in Lifespan Length and Quality
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呼吸复合物 IV 在寿命长度和质量中的作用
DOI：
10.1101/2023.06.23.546283
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Castejon-Vega B
中科院分区：
文献类型：
--
作者：
Castejon-Vega B
线粒体在寿命调节中起着关键作用，尽管其潜在的机制仍然难以捉摸。随着衰老的进展，ATP产生减少和活性氧（ROS）产生增加的受损线粒体积累，但线粒体耗竭延长了各种动物模型的寿命。我们以前的研究表明，复杂I（CI）的活动在发展中，而不是成年是至关重要的决定寿命ofDrosophilamelanogaster。尽管如此，CI缺陷的线粒体不产生过量的ROS，未能重演线粒体衰老。在这项研究中，我们专注于复合物IV（CIV），其消耗导致“老线粒体”的积累，即产生更少的ATP和更多的ROS。我们发现，CIV在长寿中的作用比CI更复杂，通过两个“机会之窗”塑造寿命。第一个窗口，由CI和CIV共享，发生在开发期间。CIV在发育过程中的小扰动会导致短命苍蝇的出现。这些果蝇表现出一种成年表型，让人想起线粒体相关疾病，主要特征是它们不能有效储存脂肪。因此，使用替代氧化酶（AOX）的CIV功能的部分互补恢复分子和生理表型。第二个窗口出现在苍蝇衰老期间，CIV缺乏会缩短寿命而不会加速衰老-苍蝇死得更早，但不会更快。值得注意的是，只有发育表型与TOR失调和改变的自噬相关，强调发育功能障碍独特地干扰营养感测和主要的细胞再循环途径。这项研究揭示了线粒体复合物IV在调节寿命方面的多方面作用，为促进健康老龄化的干预措施提供了潜在目标。
Mitochondria play a pivotal role in lifespan regulation, though the underlying mechanisms remain elusive. As ageing progresses, damaged mitochondria with reduced ATP production and increased Reactive Oxygen Species (ROS) generation accumulate, yet mitochondrial depletion extends the lifespan of various animal models. Our previous research demonstrated that complex I (CI) activity during development but not adulthood is crucial for determining the lifespan ofDrosophila melanogaster. Still, CI-deficient mitochondria do not generate excessive ROS, failing to recapitulate mitochondrial ageing. In this study, we focus on complex IV (CIV), whose depletion leads to the accumulation of “old-mitochondria”, i.e. producing less ATP and more ROS. We reveal that CIV’s role in longevity is more intricate than CI’s, shaping lifespan through two “windows of opportunity”. The first window, shared by CI and CIV, occurs during development. Small perturbations in CIV during development lead to the emergence of short-lived flies. These flies exhibit an adult phenotype reminiscent of mitochondrial- associated diseases, primarily characterised by their inability to store fat efficiently. Accordingly, partial complementation of CIV function using an alternative oxidase (AOX) restores molecular and physiological phenotypes. The second window emerges during fly senescence, where CIV deficiency curtails lifespan without hastening ageing—flies die earlier but not more rapidly. Notably, only the developmental phenotype is associated with TOR dysregulation and altered autophagy, emphasising that developmental dysfunction uniquely interferes with nutrient sensing and the main cellular recycling pathway. This study sheds light on the multifaceted role of mitochondrial complex IV in modulating lifespan, providing potential targets for interventions to foster healthy ageing.
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影响因子：
29
作者：
Bjedov I;Toivonen JM;Kerr F;Slack C;Jacobson J;Foley A;Partridge L
通讯作者：
Partridge L
影响因子：
--
作者：
Wang A;Mouser J;Pitt J;Promislow D;Kaeberlein M
通讯作者：
Kaeberlein M
影响因子：
3.7
作者：
Kemppainen E;George J;Garipler G;Tuomela T;Kiviranta E;Soga T;Dunn CD;Jacobs HT
通讯作者：
Jacobs HT
影响因子：
3.5
作者：
Kemppainen KK;Rinne J;Sriram A;Lakanmaa M;Zeb A;Tuomela T;Popplestone A;Singh S;Sanz A;Rustin P;Jacobs HT
通讯作者：
Jacobs HT
影响因子：
64.8
作者：
通讯作者：
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