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Cited by 348Lipid metabolism and biosynthesisAutophagy in Disease and TherapyLipid metabolism and disorders

Lipid droplet size directs lipolysis and lipophagy catabolism in hepatocytes

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Schott, Micah B., Weller, Shaun G., Schulze, Ryan J., Krueger, Eugene W., Drizyte-Miller, Kristina, Casey, Carol A., McNiven, Mark A.·2019·Journal of Cell Biology
DOI 10.1083/jcb.201803153PMC PMC6781454
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Abstract

Lipid droplet (LD) catabolism in hepatocytes is mediated by a combination of lipolysis and a selective autophagic mechanism called lipophagy, but the relative contributions of these seemingly distinct pathways remain unclear. We find that inhibition of lipolysis, lipophagy, or both resulted in similar overall LD content but dramatic differences in LD morphology. Inhibition of the lipolysis enzyme adipose triglyceride lipase (ATGL) resulted in large cytoplasmic LDs, whereas lysosomal inhibition caused the accumulation of numerous small LDs within the cytoplasm and degradative acidic vesicles. Combined inhibition of ATGL and LAL resulted in large LDs, suggesting that lipolysis targets these LDs upstream of lipophagy. Consistent with this, ATGL was enriched in larger-sized LDs, whereas lipophagic vesicles were restricted to small LDs as revealed by immunofluorescence, electron microscopy, and Western blot of size-separated LDs. These findings provide new evidence indicating a synergistic relationship whereby lipolysis targets larger-sized LDs to produce both size-reduced and nascently synthesized small LDs that are amenable for lipophagic internalization.

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  • Remaining lipid droplets are tagged with autophagic adapters, including SQSTM1/p62 and LC3B, and undergo lipophagic degradation in acidic vesicles.

    “Then the remaining lipid droplets are tagged with autophagic adapters, including SQSTM1/p62 and LC3B, and undergo lipophagic degradation in acidic vesicles.”

    From APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics (2026) · cites this paper as [63]

    The Results section (page unavailable) reports that small lipid droplets associate with GFP-LC3 autophagosomes and are terminally degraded by lipophagy in acidic organelles. The Discussion (page unavailable) says some may be remnants of larger droplets after lipolysis, supporting the sequence only as a possibility. The copy does not identify SQSTM1/p62 or specifically LC3B as adapters tagging those droplets. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In hepatocytes, lipid droplet catabolism occurs as a sequential, two-step process.

    “In hepatocytes, lipid droplet catabolism has been reported to occur as a sequential, two-step process63.”

    From APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics (2026) · cites this paper as [63]

  • Triglyceride-rich lipid droplets are degraded via lipolysis mediated by the rate-limiting lipase adipose triglyceride lipase (ATGL).

    “First, triglyceride-rich lipid droplets are degraded via lipolysis mediated by the rate-limiting lipase adipose triglyceride lipase (ATGL).”

    From APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics (2026) · cites this paper as [63]

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Cited by

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Authors
Schott, M. B., Weller, S. G., Schulze, R. J., Krueger, E. W., Drizyte-Miller, K., Casey, C. A., & McNiven, M. A.
Affiliations
  • Mayo Clinic (US)
  • Department of Biochemistry and Molecular Biology, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 1
  • VA Nebraska Western Iowa Health Care System (US)
Corresponding author
McNiven, Mark A.
ORCID
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2019-08-07
Volume
218
Issue
10
Pages
3320-3335
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.201803153
PMC
PMC6781454
OpenAlex
W2964451058
Cited by
348
References
1
Citations by year
2026: 48 · 2025: 68 · 2024: 59 · 2023: 49 · 2022: 50 · 2021: 45 · 2020: 25 · 2019: 4
FWCI
12.96
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (R01DK044650, R01AA020735, T32DK007352, K99AA026877)
  • Mayo Clinic (P30DK084567)
  • U.S. Department of Veterans Affairs
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords
lipid droplets, lipolysis, lipophagy, hepatocytes, adipose triglyceride lipase, lysosomal acid lipase, lipid droplet size, selective autophagy, lysosomal inhibition, lipid droplet morphology
MeSH terms
Animals, Female, Lipolysis, Triglycerides, Rats, Sprague-Dawley, Hepatocytes, Rats, Lipid Droplets

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