title: Tetracyclines Disturb Mitochondrial Function across Eukaryotic Models: A Call for Caution in Biomedical Research.
abstract: 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.
authors.affiliation: Laboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Norman
authors.initials: N
authors.lastname: Moullan
authors.affiliation: Laboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Laurent
authors.initials: L
authors.lastname: Mouchiroud
authors.affiliation: Laboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Laboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Dongryeol
authors.initials: D
authors.lastname: Ryu
authors.affiliation: Laboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Evan G
authors.initials: EG
authors.lastname: Williams
authors.affiliation: Laboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Mottis
authors.affiliation: Laboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Virginija
authors.initials: V
authors.lastname: Jovaisaite
authors.affiliation: Laboratory of Systems Biology and Genetics, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Frochaux
authors.affiliation: Laboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Quiros
authors.affiliation: Laboratory of Systems Biology and Genetics, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Bart
authors.initials: B
authors.lastname: Deplancke
authors.affiliation: Laboratory Genetic Metabolic Diseases, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands. Electronic address: r.h.houtkooper@amc.nl.
authors.forename: Riekelt H
authors.initials: RH
authors.lastname: Houtkooper
authors.affiliation: Laboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland. Electronic address: admin.auwerx@epfl.ch.
authors.forename: Johan
authors.initials: J
authors.lastname: Auwerx