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Cited by 2,740Lipid metabolism and biosynthesisCancer, Lipids, and MetabolismLipid metabolism and disorders

Dynamics and functions of lipid droplets

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Olzmann, James A., Carvalho, Pedro·2019·Nature Reviews Molecular Cell Biology
DOI 10.1038/s41580-018-0085-zPMC PMC6746329
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Abstract

Lipid droplets are storage organelles at the centre of lipid and energy homeostasis. They have a unique architecture consisting of a hydrophobic core of neutral lipids, which is enclosed by a phospholipid monolayer that is decorated by a specific set of proteins. Originating from the endoplasmic reticulum, lipid droplets can associate with most other cellular organelles through membrane contact sites. It is becoming apparent that these contacts between lipid droplets and other organelles are highly dynamic and coupled to the cycles of lipid droplet expansion and shrinkage. Importantly, lipid droplet biogenesis and degradation, as well as their interactions with other organelles, are tightly coupled to cellular metabolism and are critical to buffer the levels of toxic lipid species. Thus, lipid droplets facilitate the coordination and communication between different organelles and act as vital hubs of cellular metabolism.

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  • Filipin only stains free (unesterified) cholesterol, and cellular cholesterol accumulation is associated with excess LD.

    “Although filipin only stains free (unesterified) cholesterol, cellular cholesterol accumulation is associated with excess LD10,37,38.”

    From PICALM Alzheimer’s risk allele causes aberrant lipid droplets in microglia (2025) · cites this paper as [37]

    The ‘Neutral lipid synthesis and lens formation’ section says cholesterol can be esterified into a lipid-droplet component and that sterol esters can trigger droplet formation. This supports a connection between cholesterol storage and lipid droplets, but it does not establish that cellular cholesterol accumulation is associated with excess droplets. Our copy also does not address what filipin stains. (LLM, conf=0.77)

    Experimental — accuracy not yet measured

  • FIT2 plays a key role in LD biogenesis by facilitating LD formation from the endoplasmic reticulum.

    “FIT2, a ubiquitously expressed protein, plays a key role in LD biogenesis by facilitating LD formation from the endoplasmic reticulum (1).”

    From Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model (2025) · cites this paper as [1]

    The Lipid droplet budding section (page unavailable) identifies FIT2 as an ER membrane protein and says FIT proteins facilitate lipid-droplet budding from the ER; FIT2 mutants also fail to restore proper budding. The copy does not establish the citing sentence’s additional description of FIT2 as ubiquitously expressed. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • One route for lipid droplet turnover is via lipophagy, the selective autophagy of lipid droplets, which involves ubiquitination and binding to autophagy adapter proteins like SQSTM1/p62.

    “One route for lipid droplet turnover is via lipophagy–the selective autophagy of lipid droplets–which involves ubiquitination and binding to autophagy adapter proteins like SQSTM1/p621.”

    From APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics (2026) · cites this paper as [1]

    The ‘Lipid droplet–lysosome contacts’ section describes clearance of lipid droplets by microlipophagy, supporting lipophagy as a route for turnover. It does not say that this route involves ubiquitination or binding to SQSTM1/p62; the ‘Lipid droplets protect against ER stress’ section mentions polyubiquitylated proteins but says their location relative to droplets is unclear. Page numbers are unavailable in our copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Cholesterol esters, derived from cellular cholesterol, are often stored in LDs along with triacylglycerols (TGs).

    “Cholesterol esters, derived from cellular cholesterol, are often stored in LDs along with triacylglycerols (TGs)37.”

    From PICALM Alzheimer’s risk allele causes aberrant lipid droplets in microglia (2025) · cites this paper as [37]

  • LDs store neutral lipids including TAG and sterol esters within a phospholipid monolayer and regenerate FAs for energetic needs upon starvation.

    “These organelles store neutral lipids including TAG and sterol esters within a phospholipid monolayer and regenerate FAs for energetic needs upon starvation (Olzmann and Carvalho, 2019).”

    From ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism (2021) · cites this paper as Olzmann and Carvalho, 2019

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Cited by

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Authors
Olzmann, J. A., & Carvalho, P.
Affiliations
  • University of California, Berkeley (US)
  • University of Oxford (GB)
Corresponding author
  • Olzmann, James A.
  • Carvalho, Pedro
ORCID
Venue
Nature Reviews Molecular Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2018-12-06
Volume
20
Issue
3
Pages
137-155
ISSN
  • 1471-0072 (ISSN-L)
  • 1471-0080
DOI
10.1038/s41580-018-0085-z
PMC
PMC6746329
OpenAlex
W2903107073
Cited by
2,740
References
9
Citations by year
2026: 385 · 2025: 514 · 2024: 483 · 2023: 434 · 2022: 352 · 2021: 307 · 2020: 181 · 2019: 83
FWCI
13.96
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Reviews Molecular Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Wellcome Trust (202642/Z/16/Z)
  • Biotechnology and Biological Sciences Research Council (BB/R018375/1)
  • National Institute on Aging (R21AG056502)
  • National Institute of General Medical Sciences (R01GM112948)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords
lipid droplets, lipid homeostasis, energy homeostasis, membrane contact sites, lipid droplet formation, lipid droplet degradation, lipotoxicity, organelle interactions, endoplasmic reticulum, neutral lipids, phospholipid monolayers, lipid droplet dynamics, cellular metabolism
MeSH terms
Animals, Endoplasmic Reticulum, Homeostasis, Humans, Phospholipids, Lipid Metabolism, Lipid Droplets

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