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Cited by 188Liver Disease Diagnosis and TreatmentLipid metabolism and biosynthesisAdvanced Proteomics Techniques and Applications

Organellar proteomics and phospho-proteomics reveal subcellular reorganization in diet-induced hepatic steatosis

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Krahmer, Natalie, Najafi, Bahar, Schueder, Florian, Quagliarini, Fabiana, Steger, Martin, Seitz, Susanne, Kasper, Robert, Salinas, Favio +7 more·2018·Developmental Cell
DOI 10.1016/j.devcel.2018.09.017
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Abstract

Lipid metabolism is highly compartmentalized between cellular organelles that dynamically adapt their compositions and interactions in response to metabolic challenges. Here, we investigate how diet-induced hepatic lipid accumulation, observed in non-alcoholic fatty liver disease (NAFLD), affects protein localization, organelle organization, and protein phosphorylation in vivo. We develop a mass spectrometric workflow for protein and phosphopeptide correlation profiling to monitor levels and cellular distributions of ∼6,000 liver proteins and ∼16,000 phosphopeptides during development of steatosis. Several organelle contact site proteins are targeted to lipid droplets (LDs) in steatotic liver, tethering organelles orchestrating lipid metabolism. Proteins of the secretory pathway dramatically redistribute, including the mis-localization of the COPI complex and sequestration of the Golgi apparatus at LDs. This correlates with reduced hepatic protein secretion. Our systematic in vivo analysis of subcellular rearrangements and organelle-specific phosphorylation reveals how nutrient overload leads to organellar reorganization and cellular dysfunction.

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  • APOE was identified in subsequent studies of the lipid droplet proteome in mouse liver and THP-1 macrophages.

    “APOE was identified in subsequent studies of the LD proteome in mouse liver and THP-1 macrophages (Krahmer et al., 2018; Mejhert et al., 2020).”

    From APOE traffics to astrocyte lipid droplets and modulates triglyceride saturation and droplet size (2024) · cites this paper as Krahmer et al., 2018

    The Results and Discussion (pages unavailable) describe a mouse-liver lipid-droplet proteome, supporting the identification of Krahmer et al. as a study of that proteome. The Results also report increased levels of several apolipoproteins, but the copy does not name APOE or identify it as a lipid-droplet protein. The THP-1 macrophage portion appears to be attributed to the other citation, not this paper. (LLM, conf=0.77)

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  • Both cell type and cellular environment modulate the lipid droplet proteome and lipidome.

    “Importantly, both cell type and cellular environment modulate the lipid droplet proteome and lipidome3–9.”

    From APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics (2026) · cites this paper as [8]

    The Results report that lipid-droplet proteins change their localization under a high-fat diet, and the Discussion suggests that some may be tissue- or cell-type-specific. This supports modulation of the lipid-droplet proteome, but the cited passages do not establish that cell type and environment both modulate the lipid-droplet lipidome. (LLM, conf=0.86)

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References 54 · Cited by 188

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Authors
Krahmer, N., Najafi, B., Schueder, F., Quagliarini, F., Steger, M., Seitz, S., Kasper, R., Salinas, F., Cox, J., Uhlenhaut, N. H., Walther, T. C., Jungmann, R., Zeigerer, A., Borner, G. H. H., & Mann, M.
Affiliations
  • Max Planck Institute of Biochemistry (DE)
  • University Hospital Heidelberg (DE)
  • Center for NanoScience (DE)
  • Helmholtz Munich (DE)
  • Max Planck Institute of Neurobiology (DE)
  • Broad Institute (US)
  • University of Copenhagen (DK)
Corresponding author
Mann, Matthias
ORCID
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2018-10
Volume
47
Issue
2
Pages
205-221.e7
ISSN
1534-5807 (ISSN-L)
DOI
10.1016/j.devcel.2018.09.017
OpenAlex
W2896516599
Cited by
188
References
54
Citations by year
2026: 28 · 2025: 23 · 2024: 32 · 2023: 20 · 2022: 22 · 2021: 25 · 2020: 20 · 2019: 16 · 2018: 2
FWCI
11.97
Type
journal article
Language
en
Open access
Licence
Locations
  • Developmental Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Site cant be reached (submittedVersion, other-oa)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
  • PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
Funders
  • Yale School of Medicine
  • Deutsche Forschungsgemeinschaft (UH 275/1-1, ZE 1037/1-1)
  • National Institute of General Medical Sciences (R01GM097194)
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Keywords
hepatic steatosis, non-alcoholic fatty liver disease, lipid droplets, membrane contact sites, protein phosphorylation, secretory pathway, COPI complex, Golgi apparatus, protein secretion, subcellular protein localization
MeSH terms
Nutrients, Animals, Diet, Fatty Liver, Golgi Apparatus, Lipids, Liver, Mice, Inbred C57BL, Phosphorylation, Mass Spectrometry, Organelles, Protein Transport, Proteomics, Lipid Metabolism, Mitochondrial Membranes, Mice, Secretory Pathway, Diet, High-Fat, Lipid Droplets

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