Tetracyclines Disturb Mitochondrial Function across Eukaryotic Models: A Call for Caution in Biomedical Research.
Moullan NLaboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Mouchiroud LLaboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Wang XLaboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Ryu DLaboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Williams EGLaboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Mottis ALaboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Jovaisaite VLaboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Frochaux MVLaboratory of Systems Biology and Genetics, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Quiros PMLaboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Deplancke BLaboratory of Systems Biology and Genetics, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Houtkooper RHLaboratory Genetic Metabolic Diseases, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands. Electronic address: r.h.houtkooper@amc.nl.
Auwerx JLaboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland. Electronic address: admin.auwerx@epfl.ch.
English
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.