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Tetracyclines Disturb Mitochondrial Function across Eukaryotic Models: A Call for Caution in Biomedical Research
Norman Moullan1, Laurent Mouchiroud1, Xu Wang1
1Laboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Cell Reports
|March 17, 2015
Summary
Tetracyclines, widely used in research, disrupt mitochondrial translation, causing proteotoxic stress and altering gene expression across diverse organisms. Scientists should consider these confounding effects and limit tetracycline use due to environmental and health concerns.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Tetracyclines, including doxycycline, are extensively utilized for gene expression control via Tet-on/Tet-off systems.
- The full spectrum of direct tetracycline effects remains incompletely understood.
Purpose of the Study:
- To investigate the direct cellular and organismal effects of tetracycline antibiotics beyond their intended use in gene regulation.
- To elucidate the mechanisms by which tetracyclines impact mitochondrial function and cellular homeostasis.
Main Methods:
- Utilized Tet-on/Tet-off systems to administer tetracyclines.
- Assessed mitochondrial translation, protein imbalance, and proteotoxic stress.
- Analyzed nuclear gene expression, mitochondrial dynamics, and overall function in various model systems (cell lines, C. elegans, Drosophila, mice, plants).
Main Results:
- Tetracyclines induce a mitonuclear protein imbalance by affecting mitochondrial translation.
- These antibiotics cause mitochondrial proteotoxic stress even at low concentrations.
- Observed significant changes in nuclear gene expression, mitochondrial dynamics, and function across multiple species.
Conclusions:
- Tetracyclines possess direct, potentially confounding effects on experimental results due to mitochondrial impact.
- Widespread use of tetracyclines in research necessitates awareness of these off-target effects.
- Extensive tetracycline use in livestock warrants caution due to potential environmental and human health implications.
