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Cited by 346Biotin and Related StudiesLipid metabolism and biosynthesisLipid metabolism and disorders

A proximity labeling strategy provides insights into the composition and dynamics of lipid droplet proteomes

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Bersuker, Kirill, Peterson, Clark W.H., To, Milton, Sahl, Steffen J., Savikhin, Victoria, Grossman, Elizabeth A., Nomura, Daniel K., Olzmann, James A.·2018·Developmental Cell
DOI 10.1016/j.devcel.2017.11.020PMC PMC5764092
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Abstract

Lipid droplet (LD) functions are regulated by a complement of integral and peripheral proteins that associate with the bounding LD phospholipid monolayer. Defining the composition of the LD proteome has remained a challenge due to the presence of contaminating proteins in LD-enriched buoyant fractions. To overcome this limitation, we developed a proximity labeling strategy that exploits LD-targeted APEX2 to biotinylate LD proteins in living cells. Application of this approach to two different cell types identified the vast majority of previously validated LD proteins, excluded common contaminating proteins, and revealed new LD proteins. Moreover, quantitative analysis of LD proteome dynamics uncovered a role for endoplasmic reticulum-associated degradation in controlling the composition of the LD proteome. These data provide an important resource for future LD studies and demonstrate the utility of proximity labeling to study the regulation of LD proteomes.

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Crossref · 10.1016/j.devcel.2017.11.020

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  • Proximity ligation identified APOE as a protein on the cytoplasmic face of lipid droplets in Huh7 hepatocarcinoma cells.

    “A proximity ligation strategy identified APOE as a protein on the cytoplasmic face of LDs in Huh7 hepatocarcinoma cells (Bersuker et al., 2018).”

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

    The Results section, “An Integrated U2OS and Huh7 High-Confidence LD Proteome” (page unavailable), reports using APEX2 proximity biotinylation to identify lipid-droplet proteins in Huh7 cells. Neither that passage nor searches for APOE and apolipoprotein E identify APOE as one of those proteins or establish its location on the cytoplasmic face. The paper describes proximity labeling, not proximity ligation. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • 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 [3]

    The Results section (‘An Integrated U2OS and Huh7 High-Confidence LD Proteome’; page unavailable) says lipid droplets differ in both lipid composition and associated proteins across cell types. The Introduction says proteins are recruited to droplets in response to changes in cellular metabolism. Our copy does not establish that cellular environment also modulates the lipid droplet lipidome. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • A few of these non-canonical functions have been associated with lipid droplets in other organisms like Drosophila melanogaster and in other cell systems.

    “Interestingly, a few of these non-canonical functions have been associated with lipid droplets in other organisms like Drosophila melanogaster46,66 and in other cell systems3,9.”

    From APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics (2026) · cites this paper as [3]

  • ApoE is a droplet-associated protein found on the lipid droplet surface.

    “ApoE is also droplet-associated protein found on the LD surface (Liu et al., 2023; Bersuker et al., 2018)”

    From APOE4 reshapes the lipid droplet proteome and modulates microglial inflammatory responses (2025) · cites this paper as Bersuker et al., 2018

    The Introduction describes proteins on the lipid-droplet surface, and the Results report identifying lipid-droplet proteins, but neither passage identifies ApoE. Searches for ApoE and apolipoprotein E found no passage in our copy establishing its presence on that surface. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

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Authors
Bersuker, K., Peterson, C. W. H., To, M., Sahl, S. J., Savikhin, V., Grossman, E. A., Nomura, D. K., & Olzmann, J. A.
Affiliations
  • University of California, Berkeley (US)
  • Max Planck Institute for Biophysical Chemistry (DE)
  • SLAC National Accelerator Laboratory (US)
Corresponding author
Olzmann, James A.
ORCID
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2018-01
Volume
44
Issue
1
Pages
97-112.e7
ISSN
1534-5807 (ISSN-L)
DOI
10.1016/j.devcel.2017.11.020
PMC
PMC5764092
OpenAlex
W2779540734
Cited by
346
References
3
Citations by year
2026: 35 · 2025: 66 · 2024: 35 · 2023: 40 · 2022: 30 · 2021: 40 · 2020: 41 · 2019: 38 · 2018: 21
FWCI
14.24
Type
journal article
Language
en
Open access
Licence
Locations
  • Developmental Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • Max Planck Digital Library (submittedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
  • GRO (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
Funders
  • NIH (R00DK095921, R01GM112948, R01CA172667)
  • American Heart Association (16GRNT30870005)
  • Department of Defense
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Biotin and Related Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords
lipid droplets, lipid droplet proteome, proximity labeling, APEX2, biotinylation, protein dynamics, ER-associated degradation, phospholipid monolayers, living cells
MeSH terms
ATPases Associated with Diverse Cellular Activities, Carrier Proteins, Humans, Membrane Proteins, Staining and Labeling, Biomarkers, Proteome, Membrane Transport Proteins, Receptors, Autocrine Motility Factor, Endoplasmic Reticulum-Associated Degradation, Lipid Droplets

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