ArticleJournal of lipid research2020
The anti-tubercular activity of simvastatin is mediated by cholesterol-driven autophagy via the AMPK-mTORC1-TFEB axis.
Article in Journal of lipid research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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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.
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Who cites it
29 citing papers in PubMed, 40 citations in OpenAlex.
- Autophagy in MASLD: A Metabolic and Precision Medicine Perspective.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- Pathogenesis of Tuberculosis: Interplay Between Host Antituberculosis Immunity and Immune Evasion Strategies ofMedComm · 2026Review
- Low-dose Simvastatin protects pancreatic cancer cells by promoting mitochondrial autophagy through TFEB.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Probable role of naturally derived bergapten molecule promotes autophagy in Mycobacterium tuberculosis-infected macrophages via PI3K/Akt/mTOR pathway.Archives of microbiology · 2025Article
- Targeting Autophagy as a Strategy for Developing New Host-Directed Therapeutics Against Nontuberculous Mycobacteria.Pathogens (Basel, Switzerland) · 2025Review
- Lysosomal Stress in Cardiovascular Diseases: Therapeutic Potential of Cardiovascular Drugs and Future Directions.Biomedicines · 2025Review
- Host-directed therapy for tuberculosis.European journal of medical research · 2025Review
- Immunomodulatory effects of atorvastatin on peripheral blood mononuclear cells infected withFrontiers in immunology · 2025Article
- Combined metformin and simvastatin therapy inhibits SREBP2 maturation and alters energy metabolism in glioma.Cell death & disease · 2024Article
- Impact of statin use on COVID-19 outcomes in hospitalized patients in Saudi Arabia: a retrospective cohort study.Journal of medicine and life · 2024Article
- Autophagy and hepatic lipid metabolism: mechanistic insight and therapeutic potential for MASLD.npj metabolic health and disease · 2024Review
- Exploring and exploiting the host cell autophagy during Mycobacterium tuberculosis infection.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2023Review
- Review
- Anti-Inflammatory Effects of Lipid-Lowering Drugs and Supplements-A Narrative Review.Nutrients · 2023Review
- Cardiovascular Involvement in Tuberculosis: From Pathophysiology to Diagnosis and Complications-A Narrative Review.Diagnostics (Basel, Switzerland) · 2023Review
- Activation of mitochondrial TRAP1 stimulates mitochondria-lysosome crosstalk and correction of lysosomal dysfunction.iScience · 2022Article
- Review
- Activating Parkin-dependent mitophagy alleviates oxidative stress, apoptosis, and promotes random-pattern skin flaps survival.Communications biology · 2022Article
- CRISPR Interference Reveals That All-mBio · 2022Article
- Reply to Lai et al.The Journal of infectious diseases · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The rise of drug-resistant tuberculosis poses a major risk to public health. Statins, which inhibit both cholesterol biosynthesis and protein prenylation branches of the mevalonate pathway, increase anti-tubercular antibiotic efficacy in animal models. However, the underlying molecular mechanisms are unknown. In this study, we used an in vitro macrophage infection model to investigate simvastatin's anti-tubercular activity by systematically inhibiting each branch of the mevalonate pathway and evaluating the effects of the branch-specific inhibitors on mycobacterial growth. The anti-tubercular activity of simvastatin used at clinically relevant doses specifically targeted the cholesterol biosynthetic branch rather than the prenylation branches of the mevalonate pathway. Using Western blot analysis and AMP/ATP measurements, we found that simvastatin treatment blocked activation of mechanistic target of rapamycin complex 1 (mTORC1), activated AMP-activated protein kinase (AMPK) through increased intracellular AMP:ATP ratios, and favored nuclear translocation of transcription factor EB (TFEB). These mechanisms all induce autophagy, which is anti-mycobacterial. The biological effects of simvastatin on the AMPK-mTORC1-TFEB-autophagy axis were reversed by adding exogenous cholesterol to the cells. Our data demonstrate that the anti-tubercular activity of simvastatin requires inhibiting cholesterol biosynthesis, reveal novel links between cholesterol homeostasis, the AMPK-mTORC1-TFEB axis, and
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Registered trials
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.