ArticleScientific reports2017
Tenofovir and adefovir down-regulate mitochondrial chaperone TRAP1 and succinate dehydrogenase subunit B to metabolically reprogram glucose metabolism and induce nephrotoxicity.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Mitochondrial changes associated with viral infectious diseases in the paediatric population.Reviews in medical virology · 2021Pooled it
- A Rare Case of Myopathy Associated with Entecavir Initiation.The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy Technicians · 2026Article
- Pharmacovigilance analysis of metabolic and nutritional adverse reactions associated with entecavir and tenofovir using the FDA adverse event reporting system database.International journal of clinical pharmacy · 2025Article
- Problems in Cancer Genome Medicine: Base Mutations Cause Intron Start Signals, Resulting in Unexpected Splicing.World journal of oncology · 2025Article
- Tenofovir alafenamide promotes weight gain and impairs fatty acid metabolism-related signaling pathways in visceral fat tissue compared to tenofovir disoproxil fumarate.Antiviral research · 2025Article
- An in-depth investigation of NAs-induced osteoporosis adverse events: a real-world, network toxicology and molecular docking analysis.Frontiers in medicine · 2025Article
- Evaluation of Hippocampal Microanatomy and Neuro-Biomarkers Following Administration of Silver Nanoparticles Conjugated with Tenofovir Disoproxil Fumarate in Experimental Diabetic Rats.Pharmaceuticals (Basel, Switzerland) · 2024Article
- [Role of mitochondrial autophagy and the curative effect of rehmannia glutinosa leaves total glycoside capsules on nucleos(t)ide drug-induced renal injury].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024Article
- MCT1-governed pyruvate metabolism is essential for antibody class-switch recombination through H3K27 acetylation.Nature communications · 2024Article
- An evolving view of complex II-noncanonical complexes, megacomplexes, respiration, signaling, and beyond.The Journal of biological chemistry · 2023Review
- Current drugs for HIV-1: from challenges to potential in HIV/AIDS.Frontiers in pharmacology · 2023Review
- Human immunodeficiency virus and antiretroviral therapy-mediated immune cell metabolic dysregulation in children born to HIV-infected women: potential clinical implications.Frontiers in immunology · 2023Review
- Severe choline deficiency induces alternative splicing aberrance in optimized duck primary hepatocyte cultures.Animal bioscience · 2022Article
- 3D Spheroids of Human Primary Urine-Derived Stem Cells in the Assessment of Drug-Induced Mitochondrial Toxicity.Pharmaceutics · 2022Article
- Tenofovir-induced osteopenia and hyperparathyroidism: A case report and literature review.Frontiers in endocrinology · 2022Review
- Mapping Adverse Outcome Pathways for Kidney Injury as a Basis for the Development of Mechanism-Based Animal-Sparing Approaches to Assessment of Nephrotoxicity.Frontiers in toxicology · 2022Article
- The role of metabolic reprogramming in tubular epithelial cells during the progression of acute kidney injury.Cellular and molecular life sciences : CMLS · 2021Review
- Mitochondrial quality control in kidney injury and repair.Nature reviews. Nephrology · 2021Review
- Immunometabolism and HIV-1 pathogenesis: food for thought.Nature reviews. Immunology · 2021Review
- FOSL2 Is Involved in the Regulation of Glycogen Content in Chicken Breast Muscle Tissue.Frontiers in physiology · 2021Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the therapeutic success of tenofovir (TFV) for treatment of HIV-1 infection, numerous cases of nephrotoxicity have been reported. Mitochondrial toxicity has been purported as the major target of TFV-associated renal tubulopathy but the underlying molecular mechanism remains unclear. In this report, we use metabolomics and proteomics with HK-2 cells and animal models to dissect the molecular pathways underlying nephropathy caused by TFV and its more toxic analog, adefovir (ADV). Proteomic analysis shows that mitochondrial chaperone TRAP1 and mtDNA replicating protein SSBP1 were significantly down-regulated in TFV and ADV treated HK-2 cells compared with controls. Transmission electron microscopy (TEM) revealed that TFV and ADV-treated HK-2 cells had accumulated glycogen, a phenotype that was also observed in mice treated with TFV and ADV. Analysis of the proteins in TCA cycle showed succinate dehydrogenase subunit B (SDHB) was nearly depleted in glucose oxidative phosphorylation pathway however certain enzymes in the glycolysis and glycogen synthesis pathway had elevated expression in TFV and ADV-treated HK-2 cells. These results suggest that TFV and ADV may cause mitochondrial dysfunction in renal tubular cells and reprogramming of glucose metabolism. The resulting glycogen accumulation may partially contribute to TFV and ADV induced renal dysfunction.
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