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

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2015 Mar 17

PMID 25772356

Citations 245

Authors

Norman Moullan

Laurent Mouchiroud

Xu Wang

Dongryeol Ryu

Evan G Williams

Adrienne Mottis

Virginija Jovaisaite

Michael V Frochaux

Pedro M Quiros

Bart Deplancke

Riekelt H Houtkooper

Johan Auwerx

Affiliations

Soon will be listed here.

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.

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