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Cited by 279Cellular transport and secretionLipid metabolism and biosynthesisAutophagy in Disease and Therapy

VAPs and ACBD5 tether peroxisomes to the ER for peroxisome maintenance and lipid homeostasis.

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Hua, Rong, Cheng, Derrick, Coyaud, Étienne, Freeman, Spencer, Di Pietro, Erminia, Wang, Yuqing, Vissa, Adriano, Yip, Christopher M. +6 more·2017·Journal of Cell Biology
DOI 10.1083/jcb.201608128PMC PMC5294787
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Abstract

Lipid exchange between the endoplasmic reticulum (ER) and peroxisomes is necessary for the synthesis and catabolism of lipids, the trafficking of cholesterol, and peroxisome biogenesis in mammalian cells. However, how lipids are exchanged between these two organelles is not understood. In this study, we report that the ER-resident VAMP-associated proteins A and B (VAPA and VAPB) interact with the peroxisomal membrane protein acyl-CoA binding domain containing 5 (ACBD5) and that this interaction is required to tether the two organelles together, thereby facilitating the lipid exchange between them. Depletion of either ACBD5 or VAP expression results in increased peroxisome mobility, suggesting that VAP–ACBD5 complex acts as the primary ER–peroxisome tether. We also demonstrate that tethering of peroxisomes to the ER is necessary for peroxisome growth, the synthesis of plasmalogen phospholipids, and the maintenance of cellular cholesterol levels. Collectively, our data highlight the importance of VAP–ACBD5–mediated contact between the ER and peroxisomes for organelle maintenance and lipid homeostasis.

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  • The phospholipid deficiency in ACBD5-deficient cells extends to phosphatidylethanolamine-ether and phosphatidylcholine-ether phospholipids, pointing to a general phospholipid biosynthesis defect including a general decrease in phosphatidylethanolamine-plasmalogens.

    “This phospholipid deficiency extends to phosphatidylethanolamine-ether and phosphatidylcholine-ether phospholipids, and therefore pointing to a general phospholipid biosynthesis defect, including a general decrease in phosphatidylethanolamine-plasmalogens (Hua et al., 2017; Herzog et al., 2018).”

    From The neurological pathology of peroxisomal ACBD5 deficiency – lessons from patients and mouse models (2025) · cites this paper as Hua et al., 2017

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  • In response to siRNA-mediated knockdown of ACBD5 and/or VAP proteins in HeLa cells, reductions in cellular cholesterol levels were reported.

    “In response to the siRNA mediated knockdown of ACBD5 and/or VAP proteins in HeLa cells reductions in cellular cholesterol levels were reported (Hua et al., 2017).”

    From The neurological pathology of peroxisomal ACBD5 deficiency – lessons from patients and mouse models (2025) · cites this paper as Hua et al., 2017

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Authors
Hua, R., Cheng, D., Coyaud, É., Freeman, S., Di Pietro, E., Wang, Y., Vissa, A., Yip, C. M., Fairn, G. D., Braverman, N., Brumell, J. H., Trimble, W. S., Raught, B., & Kim, P. K.
Affiliations
  • University of Toronto (CA)
  • University Health Network (CA)
  • Hospital for Sick Children (CA)
  • Department of Pediatrics and Human Genetics, Research Institute of the McGill University Health Center and McGill University, Montreal, Quebec H4A 3J1, Canada 8
  • McGill University Health Centre (CA)
Corresponding author
Kim, Peter K.
ORCID
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2017-01-20
Volume
216
Issue
2
Pages
367-377
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.201608128
PMC
PMC5294787
OpenAlex
W2579583537
Cited by
279
References
2
Citations by year
2026: 23 · 2025: 25 · 2024: 23 · 2023: 30 · 2022: 40 · 2021: 24 · 2020: 32 · 2019: 33 · 2018: 31 · 2017: 17
FWCI
16.50
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • Natural Sciences and Engineering Research Council of Canada
  • Canadian Institutes of Health Research
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
VAPA, VAPB, lipid exchange, peroxisome biogenesis, plasmalogen synthesis, cholesterol homeostasis, lipid homeostasis
MeSH terms
Animals, Chlorocebus aethiops, Cholesterol, Endoplasmic Reticulum, HeLa Cells, Homeostasis, Humans, Intracellular Membranes, Membrane Proteins, Phospholipids, Time Factors, Transfection, Signal Transduction, Microscopy, Confocal, COS Cells, Peroxisomes, Vesicular Transport Proteins, RNA Interference, Adaptor Proteins, Signal Transducing, Protein Interaction Domains and Motifs, HEK293 Cells

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