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The large GTPase Sey1/atlastin mediates lipid droplet- and FadL-dependent intracellular fatty acid metabolism of Legionella pneumophila
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Abstract
The amoeba-resistant bacterium Legionella pneumophila causes Legionnaires’ disease and employs a type IV secretion system (T4SS) to replicate in the unique, ER-associated Legionella -containing vacuole (LCV). The large fusion GTPase Sey1/atlastin is implicated in ER dynamics, ER-derived lipid droplet (LD) formation, and LCV maturation. Here, we employ cryo-electron tomography, confocal microscopy, proteomics, and isotopologue profiling to analyze LCV-LD interactions in the genetically tractable amoeba Dictyostelium discoideum . Dually fluorescence-labeled D. discoideum producing LCV and LD markers revealed that Sey1 as well as the L. pneumophila T4SS and the Ran GTPase activator LegG1 promote LCV-LD interactions. In vitro reconstitution using purified LCVs and LDs from parental or Δ sey1 mutant D. discoideum indicated that Sey1 and GTP promote this process. Sey1 and the L. pneumophila fatty acid transporter FadL were implicated in palmitate catabolism and palmitate-dependent intracellular growth. Taken together, our results reveal that Sey1 and LegG1 mediate LD- and FadL-dependent fatty acid metabolism of intracellular L. pneumophila .
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Metadata
- Authors
- Hüsler, D., Stauffer, P., Keller, B., Böck, D., Steiner, T., Ostrzinski, A., Vormittag, S., Striednig, B., Swart, A. L., Letourneur, F., Maaß, S., Becher, D., Eisenreich, W., Pilhofer, M., & Hilbi, H.
- Affiliations
- University of Zurich (CH)
- ETH Zurich (CH)
- Technical University of Munich (DE)
- Universität Greifswald (DE)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Hilbi, Hubert
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2023-05-09
- Volume
- 12
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC10259473
- OpenAlex
- W4375955037
- Cited by
- 18
- References
- 2
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 7 · 2023: 1
- FWCI
- 3.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
- ETH Zürich Research Collection
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A_175557, 310030_207826)
- NOMIS Stiftung
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Legionella and Acanthamoeba research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- Legionella pneumophila, lipid droplets, fatty acid metabolism, type IV secretion system, Legionella-containing vacuole, Ran GTPase, Dictyostelium discoideum, ER dynamics, GTPase
- MeSH terms
- Bacterial Proteins, Dictyostelium, Humans, Legionella, Legionnaires' Disease, Macrophages, Vacuoles, Legionella pneumophila, GTP Phosphohydrolases, Lipid Droplets
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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