Tetracyclines Disturb Mitochondrial Function across Eukaryotic Models: A Call for Caution in Biomedical Research.
Tetracyclines Disturb Mitochondrial Function across Eukaryotic Models: A Call for Caution in Biomedical Research.
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DOI：
10.1016/j.celrep.2015.02.034
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发表时间：
2015-03-17
期刊：
影响因子：
8.8
通讯作者：
Auwerx J
中科院分区：
文献类型：
--
作者：
Moullan N;Mouchiroud L;Wang X;Ryu D;Williams EG;Mottis A;Jovaisaite V;Frochaux MV;Quiros PM;Deplancke B;Houtkooper RH;Auwerx J
近年来，通过Tet-On/Tet-Off系统，四环素类药物如强力环素已被广泛用于控制基因表达。然而，四环素的广泛直接影响尚未得到充分认识。我们在这里表明，这些抗生素通过它们对线粒体翻译的影响而诱导有丝分裂蛋白失衡，这种影响可能反映了线粒体和蛋白细菌之间的进化关系。四环素类药物，即使在低浓度下，也会诱导线粒体蛋白毒性应激，导致核基因表达的变化，并改变常用细胞类型以及蠕虫、苍蝇、小鼠和植物的线粒体动力学和功能。由于四环素在研究中的应用如此广泛，科学家们应该意识到它们对实验结果的潜在混杂影响。此外，这些结果警告不要在牲畜中广泛使用四环素，因为这可能会对环境和人类健康产生下游影响。
In recent years, tetracyclines, such as doxycycline, have become broadly used to control gene expression by virtue of the Tet-On/Tet-Off systems. The wide range of direct effects of tetracycline use has, however, not been fully appreciated. We show here that these antibiotics induce a mitonuclear protein imbalance through their effects on mitochondrial translation, an effect that likely reflects the evolutionary relationship between mitochondria and proteobacteria. Tetracyclines, Even at low concentrations, tetracyclines induce mitochondrial proteotoxic stress, leading to changes in nuclear gene expression and altered mitochondrial dynamics and function in commonly used cell types, as well as worms, flies, mice, and plants. Since tetracyclines are so widely applied in research, scientists should be aware of their potentially confounding effects on experimental results. Furthermore, these results caution against extensive use of tetracyclines in livestock due to potential downstream impacts on the environment and human health.