Evidence map›Paper›PMID 26475870›Full record

ReviewCancer research2015

Tetracycline antibiotics impair mitochondrial function and its experimental use confounds research.

Iliana A Chatzispyrou, Ntsiki M Held, Laurent Mouchiroud, Johan Auwerx, Riekelt H Houtkooper

Open access · bronzeAbstract readReview
In one paragraph

Review in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 1 pooled it
3.9field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

81 citing papers in PubMed, 1 synthesis or guideline pooled it, 140 citations in OpenAlex.

  1. Pooled it
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  3. Ewing Sarcoma-Specific (Re)Expression Models.Methods in molecular biology (Clifton, N.J.) · 2027
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21 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 2 countries.

Iliana A ChatzispyrouLaboratory Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, the Netherlands.
Ntsiki M HeldLaboratory Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, the Netherlands.
Laurent MouchiroudLaboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Johan AuwerxLaboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. r.h.houtkooper@amc.nl admin.auwerx@epfl.ch.
Riekelt H HoutkooperLaboratory Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, the Netherlands. r.h.houtkooper@amc.nl admin.auwerx@epfl.ch.
Amsterdam UMC Location University of Amsterdam · NLÉcole Polytechnique Fédérale de Lausanne · CH

Funding

Translational Systems Genetics of Mitochondria, Metabolism, and AgingR01AG043930 · NIA · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI WILLIAMS, ROBERT W. · 2013 to 2017
$2.5M
European Research Council 638290NIA NIH HHS R01 AG043930NIA NIH HHS R01AG043930
6 · The paper itself

Abstract

Tetracyclines, a class of antibiotics that target bacterial translation, are commonly used in research for inducible gene expression using Tet-ON/Tet-OFF systems. However, such tetracycline-inducible systems carry a risk. Given that mitochondria have a "bacterial" ancestry, these antibiotics also target mitochondrial translation and impair mitochondrial function. Indeed, treatment with doxycycline-a tetracycline derivative-disturbs mitochondrial proteostasis and metabolic activity, and induces widespread gene-expression changes. Together, this affects physiology in well-established model systems ranging from cultured cells to simple organisms and to mice and plants. These changes are observed with doxycycline doses that are widely used to regulate gene expression. In light of these findings, and bearing in mind the conserved role of mitochondria in metabolism and whole organism homeostasis, we caution against the use of tetracyclines in experimental approaches. The use of newly developed tetracycline-based systems that are more sensitive could be an alternative; however, even if no overt mitochondrial toxicity is detected, widespread changes in gene expression may sensitize cells to the intended tetracycline-controlled loss or gain of function, thereby introducing a "two-hit model." This is highly relevant for cancer research, as mitochondrial metabolism holds a central position in the reallocation of nutrients for biomass production known as the Warburg effect.

Indexed as

AnimalsAnti-Bacterial AgentsDoxycyclineHumansMiceMitochondriaProtein BiosynthesisProtein Synthesis InhibitorsAnti-Bacterial AgentsDoxycyclineProtein Synthesis Inhibitors

Identifiers

PMID26475870
PMCPMC4631686
OpenAlexW1959897390

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.