Mifepristone and rapamycin have non-additive benefits for life span in mated female Drosophila.

IF 2.4 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Fly Pub Date : 2024-12-01 Epub Date: 2024-10-23 DOI:10.1080/19336934.2024.2419151
Gary N Landis, Britta Baybutt, Shoham Das, Yijie Fan, Kate Olsen, Karissa Yan, John Tower
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引用次数: 0

Abstract

The drugs mifepristone and rapamycin were compared for their relative ability to increase the life span of mated female Drosophila melanogaster. Titration of rapamycin indicated an optimal concentration of approximately 50 μM, which increased median life span here by average +81%. Meta-analysis of previous mifepristone titrations indicated an optimal concentration of approximately 466 μM, which increased median life span here by average +114%. Combining mifepristone with various concentrations of rapamycin did not produce further increases in life span, and instead reduced life span relative to either drug alone. Assay of maximum midgut diameter indicated that rapamycin was equally efficacious as mifepristone in reducing mating-induced midgut hypertrophy. The mito-QC mitophagy reporter is a previously described green fluorescent protein (GFP)-mCherry fusion protein targeted to the outer mitochondrial membrane. Inhibition of GFP fluorescence by the acidic environment of the autophagolysosome yields an increased red/green fluorescence ratio indicative of increased mitophagy. Creation of a multi-copy mito-QC reporter strain facilitated assay in live adult flies, as well as in dissected midgut tissue. Mifepristone was equally efficacious as rapamycin in activating the mito-QC mitophagy reporter in the adult female fat-body and midgut. The data suggest that mifepristone and rapamycin act through a common pathway to increase mated female Drosophila life span, and implicate increased mitophagy and decreased midgut hypertrophy in that pathway.

米非司酮和雷帕霉素对交配雌果蝇的寿命具有非叠加效益。
比较了米非司酮和雷帕霉素这两种药物增加交配雌果蝇寿命的相对能力。雷帕霉素的滴定结果表明,最佳浓度约为 50 μM,可使中位寿命平均延长 81%。对以往米非司酮滴定结果的 Meta 分析表明,最佳浓度约为 466 μM,可使中位寿命平均延长 114%。将米非司酮与不同浓度的雷帕霉素结合使用并不能进一步延长寿命,反而会比单独使用其中一种药物缩短寿命。对中肠最大直径的测定表明,雷帕霉素与米非司酮在减少交配诱导的中肠肥大方面具有同等功效。mito-QC有丝分裂报告物是一种先前描述过的针对线粒体外膜的绿色荧光蛋白(GFP)-mCherry融合蛋白。自噬溶酶体的酸性环境抑制了 GFP 的荧光,导致红/绿荧光比率增加,表明有丝分裂增加。多拷贝有丝分裂-QC报告菌株的建立有助于在活体成蝇和解剖的中肠组织中进行检测。在激活成年雌蝇脂肪体和中肠中的mito-QC有丝分裂报告基因方面,米非司酮与雷帕霉素同样有效。这些数据表明,米非司酮和雷帕霉素通过一个共同的途径来延长交配雌果蝇的寿命,并且在这一途径中增加了有丝分裂和减少了中肠肥大。
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来源期刊
Fly
Fly 生物-生化与分子生物学
CiteScore
2.90
自引率
0.00%
发文量
17
审稿时长
>12 weeks
期刊介绍: Fly is the first international peer-reviewed journal to focus on Drosophila research. Fly covers a broad range of biological sub-disciplines, ranging from developmental biology and organogenesis to sensory neurobiology, circadian rhythm and learning and memory, to sex determination, evolutionary biology and speciation. We strive to become the “to go” resource for every researcher working with Drosophila by providing a forum where the specific interests of the Drosophila community can be discussed. With the advance of molecular technologies that enable researchers to manipulate genes and their functions in many other organisms, Fly is now also publishing papers that use other insect model systems used to investigate important biological questions. Fly offers a variety of papers, including Original Research Articles, Methods and Technical Advances, Brief Communications, Reviews and Meeting Reports. In addition, Fly also features two unconventional types of contributions, Counterpoints and Extra View articles. Counterpoints are opinion pieces that critically discuss controversial papers questioning current paradigms, whether justified or not. Extra View articles, which generally are solicited by Fly editors, provide authors of important forthcoming papers published elsewhere an opportunity to expand on their original findings and discuss the broader impact of their discovery. Extra View authors are strongly encouraged to complement their published observations with additional data not included in the original paper or acquired subsequently.
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