Tetracyclines Disturb Mitochondrial Function across Eukaryotic Models: A Call for Caution in Biomedical Research

• Published in: Cell reports (Cambridge) Vol. 10; no. 10; pp. 1681 - 1691
• Main Authors: Moullan, Norman, Mouchiroud, Laurent, Wang, Xu, Ryu, Dongryeol, Williams, Evan G., Mottis, Adrienne, Jovaisaite, Virginija, Frochaux, Michael V., Quiros, Pedro M., Deplancke, Bart, Houtkooper, Riekelt H., Auwerx, Johan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.03.2015; Elsevier
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2015.02.034

In recent years, tetracyclines, such as doxycycline, have become broadly used to control gene expression by virtue of the Tet-on/Tet-off systems. However, the wide range of direct effects of tetracycline use has 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. 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. Given that 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. [Display omitted] •Tetracyclines promote mitonuclear protein imbalance and mitochondrial dysfunction•The effects of tetracyclines are conserved across eukaryotic kingdoms•Use of tetracyclines in research can confound the experimental outcome•Tetracyclines delay plant growth and may pose an environmental hazard The bacterial origins of mitochondria explain why they may be vulnerable to antibiotics such as the tetracyclines. Moullan et al. demonstrate that low concentrations of tetracyclines inhibit mitochondrial function across different species. This effect of tetracyclines can potentially confound experimental outcomes, and the data suggest a potential negative impact on the environment and health that should be further explored.