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

Rong Hua, Derrick Cheng, Étienne Coyaud, Spencer Freeman, Erminia Di Pietro, Yuqing Wang, Adriano Vissa, Christopher M. Yip, Gregory D. Fairn, Nancy Braverman, John H. Brumell, William S. Trimble, Brian Raught, Peter K. Kim

Research output: Contribution to journalArticlepeer-review

209 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)367-377
Number of pages11
JournalJournal of Cell Biology
Volume216
Issue number2
DOIs
Publication statusPublished - 2017
Externally publishedYes

Bibliographical note

Funding Information:
The work in this study is funded by the Natural Sciences and Engineering Research Council of Canada and a Canadian Institutes of Health Research project grant to P.K. Kim. The authors declare no competing financial interests.

Publisher Copyright:
© 2017 Hua et al.

ASJC Scopus Subject Areas

  • Cell Biology

PubMed: MeSH publication types

  • Journal Article

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