ArticleGenetics2010
The antidepressant sertraline targets intracellular vesiculogenic membranes in yeast.
Article in Genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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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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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.
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Who cites it
37 citing papers in PubMed, 54 citations in OpenAlex.
- Pharmacometabolomic mapping of early biochemical changes induced by sertraline and placebo.Translational psychiatry · 2013Trial
- The dual role of sertraline: From antidepressant to antifungal drug with broad metabolic disruption.Genetics and molecular biology · 2026Article
- Therapeutic Repurposing of Sertraline: Evidence for Its Antifungal Activity from In Vitro, In Vivo, and Clinical Studies.Microorganisms · 2025Review
- A cationic amphiphilic drug synergizes with strobilurin fungicides to control fungal-borne plant diseases.Cell chemical biology · 2025Article
- The Antidepressant Sertraline Modulates Gene Expression and Alternative Splicing Events in the DermatophyteGenes · 2025Article
- Fast-evolving cofactors regulate the role of HEATR5 complexes in intra-Golgi trafficking.The Journal of cell biology · 2024Article
- Two functionally distinct HEATR5 protein complexes are defined by fast-evolving co-factors in yeast.bioRxiv : the preprint server for biology · 2023Article
- Anti-Candidal Activity of Reboxetine and Sertraline Antidepressants: Effects on Pre-Formed Biofilms.Antibiotics (Basel, Switzerland) · 2023Article
- The Antidepressant Sertraline Affects Cell Signaling and Metabolism inJournal of fungi (Basel, Switzerland) · 2023Article
- Synergism between the Antidepressant Sertraline and Caspofungin as an Approach to Minimise the Virulence and Resistance in the DermatophyteJournal of fungi (Basel, Switzerland) · 2022Article
- The Antidepressant Sertraline Induces the Formation of Supersized Lipid Droplets in the Human PathogenJournal of fungi (Basel, Switzerland) · 2022Article
- Effects of pH on the Properties of Membrane Vesicles Including Glucosyltransferase inMicroorganisms · 2021Article
- A Yeast-Based Screening Unravels Potential Therapeutic Molecules for Mitochondrial Diseases Associated with DominantInternational journal of molecular sciences · 2021Article
- Apoptotic Bodies: Mechanism of Formation, Isolation and Functional Relevance.Sub-cellular biochemistry · 2021Article
- Thermodynamics of selective serotonin reuptake inhibitors partitioning into 1,2-dioleoyl-RSC advances · 2020Article
- Synergistic and antagonistic drug interactions in the treatment of systemic fungal infections.eLife · 2020Article
- Pharmacokinetics-pharmacodynamics of sertraline as an antifungal in HIV-infected Ugandans with cryptococcal meningitis.Journal of pharmacokinetics and pharmacodynamics · 2019Article
- Effects of Complex DNA and MVs with GTF Extracted fromMolecules (Basel, Switzerland) · 2019Article
- Adaptor protein complex-1 (AP-1) is recruited by the HEATR5 protein Laa1 and its co-factor Laa2 in yeast.The Journal of biological chemistry · 2019Article
- A simple and inexpensive quantitative technique for determining chemical sensitivity in Saccharomyces cerevisiae.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Numerous studies have shown that the clinical antidepressant sertraline (Zoloft) is biologically active in model systems, including fungi, which do not express its putative protein target, the serotonin/5-HT transporter, thus demonstrating the existence of one or more secondary targets. Here we show that in the absence of its putative protein target, sertraline targets phospholipid membranes that comprise the acidic organelles of the intracellular vesicle transport system by a mechanism consistent with the bilayer couple hypothesis. On the basis of a combination of drug-resistance selection and chemical-genomic screening, we hypothesize that loss of vacuolar ATPase activity reduces uptake of sertraline into cells, whereas dysregulation of clathrin function reduces the affinity of membranes for sertraline. Remarkably, sublethal doses of sertraline stimulate growth of mutants with impaired clathrin function. Ultrastructural studies of sertraline-treated cells revealed a phenotype that resembles phospholipidosis induced by cationic amphiphilic drugs in mammalian cells. Using reconstituted enzyme assays, we also demonstrated that sertraline inhibits phospholipase A(1) and phospholipase D, exhibits mixed effects on phospholipase C, and activates phospholipase A(2). Overall, our study identifies two evolutionarily conserved membrane--active processes-vacuolar acidification and clathrin-coat formation--as modulators of sertraline's action at membranes.
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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.