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Cited by 106Cellular transport and secretionLipid metabolism and biosynthesisAutophagy in Disease and Therapy

Identification of two pathways mediating protein targeting from ER to lipid droplets

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Song, Jiunn, Mizrak, Arda, Lee, Chia-Wei, Cicconet, Marcelo, Lai, Zon Weng, Tang, Wei-Chun, Lu, Chieh-Han, Mohr, Stephanie E. +2 more·2022·Nature Cell Biology
DOI 10.1038/s41556-022-00974-0PMC PMC9481466

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Abstract

Pathways localizing proteins to their sites of action are essential for eukaryotic cell organization and function. Although mechanisms of protein targeting to many organelles have been defined, how proteins, such as metabolic enzymes, target from the endoplasmic reticulum (ER) to cellular lipid droplets (LDs) is poorly understood. Here we identify two distinct pathways for ER-to-LD protein targeting: early targeting at LD formation sites during formation, and late targeting to mature LDs after their formation. Using systematic, unbiased approaches in Drosophila cells, we identified specific membrane-fusion machinery, including regulators, a tether and SNARE proteins, that are required for the late targeting pathway. Components of this fusion machinery localize to LD–ER interfaces and organize at ER exit sites. We identified multiple cargoes for early and late ER-to-LD targeting pathways. Our findings provide a model for how proteins target to LDs from the ER either during LD formation or by protein-catalysed formation of membrane bridges.

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Cited by

Sorted by citations

Authors
Song, J., Mizrak, A., Lee, C.-W., Cicconet, M., Lai, Z. W., Tang, W.-C., Lu, C.-H., Mohr, S. E., Farese, R. V., & Walther, T. C.
Affiliations
  • Harvard University (US)
  • Howard Hughes Medical Institute (US)
  • Broad Institute (US)
Corresponding author
  • Farese, Robert V.
  • Walther, Tobias C.
ORCID
Venue
Nature Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2022-09
Volume
24
Issue
9
Pages
1364-1377
ISSN
  • 1465-7392 (ISSN-L)
  • 1476-4679
DOI
10.1038/s41556-022-00974-0
PMC
PMC9481466
OpenAlex
W4294051554
Cited by
106
References
1
Citations by year
2026: 25 · 2025: 32 · 2024: 31 · 2023: 14 · 2022: 4
FWCI
11.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Cell Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Howard Hughes Medical Institute
  • American Heart Association
  • National Institutes of Health (TL1TR001101, GM132087)
  • National Institute of General Medical Sciences (GM132087, P41GM132087, T32GM007753, R01GM097194)
  • National Center for Advancing Translational Sciences
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
protein targeting, lipid droplets, endoplasmic reticulum, membrane fusion, SNARE proteins, ER exit sites, lipid droplet formation, Drosophila cells, organelle targeting
MeSH terms
Animals, Drosophila, Endoplasmic Reticulum, Protein Transport, Lipid Metabolism, SNARE Proteins, Lipid Droplets

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