ArticleThe Journal of clinical investigation2022
Tetracycline-induced mitohormesis mediates disease tolerance against influenza.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 44 citations in OpenAlex.
- A functional genomics-pharmacotranscriptomics framework identifies host-directed anti-influenza agents.iScience · 2026Article
- Atypical Tetracyclines Promote Longevity and Ferroptotic Neuroprotection via Translation Attenuation.Aging cell · 2026Article
- Review
- Targeting Mitochondrial Stress Responses: Terbinafine and Miglustat as Novel Lifespan and Healthspan Modulators.Aging cell · 2026Article
- Differential disease tolerance mediates sex-biased illness severity in sepsis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Atypical tetracyclines promote longevity and ferroptotic neuroprotection via translation attenuation.bioRxiv : the preprint server for biology · 2026Article
- Omadacycline - Associated Anticardiolipin Antibody Positivity and Hypercoagulable State: A Case Report and Review of Tetracycline - Induced Immune Dysregulation.Infection and drug resistance · 2026Article
- Network-based prediction and real-world patient data observation identify doxycycline as a repurposable drug in Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Direct and transgenerational effects of tetracyclines on the microbiome, transcriptome, and male mating behavior of the sheep blowfly Lucilia cuprina.G3 (Bethesda, Md.) · 2025Article
- Treatment with mitochondrial targeting antibiotics improves survival outcomes after Flock House virus infection in young and aged Drosophila melanogaster.Research square · 2025Article
- Astragaloside IV mitigates influenza-induced inflammatory responses by suppressing the Wnt/β-catenin signalling pathway in alveolar macrophages.Veterinary research · 2025Article
- Oxytetracycline and its Non-Antibiotic Derivative DOT Protect Midbrain Dopamine Neurons from Iron-Driven Oxidative Damage.Neurotoxicity research · 2025Article
- Mitochondrial genetics, signalling and stress responses.Nature cell biology · 2025Review
- A naturally occurring mitochondrial genome variant confers broad protection from infection in Drosophila.PLoS genetics · 2024Article
- Response by Gao et al to Letter Regarding Article, "Reduced Mitochondrial Protein Translation Promotes Cardiomyocyte Proliferation and Heart Regeneration".Circulation · 2024Article
- How did antibiotic growth promoters increase growth and feed efficiency in poultry?Poultry science · 2024Article
- Proteomic Analysis of the Mitochondrial Responses in P19 Embryonic Stem Cells Exposed to Florfenicol.Toxics · 2023Article
- Mitohormesis.Cell metabolism · 2023Review
- Article
- Rescue of Dopamine Neurons from Iron-Dependent Ferroptosis by Doxycycline and Demeclocycline and Their Non-Antibiotic Derivatives.Antioxidants (Basel, Switzerland) · 2023Article
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitohormesis defines the increase in fitness mediated by adaptive responses to mild mitochondrial stress. Tetracyclines inhibit not only bacterial but also mitochondrial translation, thus imposing a low level of mitochondrial stress on eukaryotic cells. We demonstrate in cell and germ-free mouse models that tetracyclines induce a mild adaptive mitochondrial stress response (MSR), involving both the ATF4-mediated integrative stress response and type I interferon (IFN) signaling. To overcome the interferences of tetracyclines with the host microbiome, we identify tetracycline derivatives that have minimal antimicrobial activity, yet retain full capacity to induce the MSR, such as the lead compound, 9-tert-butyl doxycycline (9-TB). The MSR induced by doxycycline (Dox) and 9-TB improves survival and disease tolerance against lethal influenza virus (IFV) infection when given preventively. 9-TB, unlike Dox, did not affect the gut microbiome and also showed encouraging results against IFV when given in a therapeutic setting. Tolerance to IFV infection is associated with the induction of genes involved in lung epithelial cell and cilia function, and with downregulation of inflammatory and immune gene sets in lungs, liver, and kidneys. Mitohormesis induced by non-antimicrobial tetracyclines and the ensuing IFN response may dampen excessive inflammation and tissue damage during viral infections, opening innovative therapeutic avenues.
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