Differential roles for ACBD4 and ACBD5 in peroxisome-ER interactions and lipid metabolism
dc.contributor.author | Costello, JL | |
dc.contributor.author | Koster, J | |
dc.contributor.author | Silva, BSC | |
dc.contributor.author | Worthy, HL | |
dc.contributor.author | Schrader, TA | |
dc.contributor.author | Hacker, C | |
dc.contributor.author | Passmore, J | |
dc.contributor.author | Kuypers, FA | |
dc.contributor.author | Waterham, HR | |
dc.contributor.author | Schrader, M | |
dc.date.accessioned | 2023-07-05T14:57:52Z | |
dc.date.issued | 2023-07-04 | |
dc.date.updated | 2023-07-05T14:31:00Z | |
dc.description.abstract | Peroxisomes and the endoplasmic reticulum (ER) are intimately linked subcellular organelles, physically connected at membrane contact sites. As well as collaborating in lipid metabolism, e.g. of very long chain fatty acids (VLCFAs) and plasmalogens, the ER also plays a role in peroxisome biogenesis. Recent work has identified tethering complexes on the ER and peroxisome membranes which connect the organelles. These include membrane contacts formed via interactions between the ER protein VAPB (vesicle-associated membrane proteinassociated protein B) and the peroxisomal proteins ACBD4 and ACBD5 (acyl-coenzyme Abinding domain protein). Loss of ACBD5 has been shown to cause a significant reduction in peroxisome-ER contacts and accumulation of VLCFAs. However, the role of ACBD4, and the relative contribution these two proteins make to contact site formation and recruitment of VLCFAs to peroxisomes remains unclear. Here, we address these questions, using a combination of molecular cell biology, biochemical and lipidomics analyses following loss of ACBD4 or ACBD5 in HEK293 cells. We show that the tethering function of ACBD5 is not absolutely required for efficient peroxisomal β-oxidation of VLCFAs. We demonstrate that loss of ACBD4 does not reduce peroxisome-ER connections or result in accumulation of VLCFAs. Instead, the loss of ACBD4 resulted in an increase in the rate of β-oxidation of VLCFAs. Finally, we observe interaction between ACBD5 and ACBD4, independent of VAPB binding. Overall, our findings suggest that ACBD5 may act as a primary tether and VLCFA recruitment factor, whereas ACBD4 may have regulatory functions in peroxisomal lipid metabolism at the peroxisome-ER interface. | en_GB |
dc.description.sponsorship | Biotechnology & Biological Sciences Research Council (BBSRC) | en_GB |
dc.description.sponsorship | UK Research and Innovation | en_GB |
dc.description.sponsorship | Royal Society | en_GB |
dc.description.sponsorship | European Union Horizon 2020 | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.identifier.citation | Article 105013 | en_GB |
dc.identifier.doi | https://doi.org/10.1016/j.jbc.2023.105013 | |
dc.identifier.grantnumber | BB/V018167/1 | en_GB |
dc.identifier.grantnumber | BB/T002255/1 | en_GB |
dc.identifier.grantnumber | BB/N01541X/1 | en_GB |
dc.identifier.grantnumber | BB/W015420/1 | en_GB |
dc.identifier.grantnumber | MR/T019409/1 | en_GB |
dc.identifier.grantnumber | RGS\R2\192378 | en_GB |
dc.identifier.grantnumber | 812968 PERICO | en_GB |
dc.identifier.grantnumber | 08135 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/133552 | |
dc.identifier | ORCID: 0000-0002-2867-1864 (Costello, Joseph L) | |
dc.identifier | ORCID: 0000-0001-8497-0773 (Worthy, Harley L) | |
dc.language.iso | en | en_GB |
dc.publisher | Elsevier / American Society for Biochemistry and Molecular Biology | en_GB |
dc.rights | © 2023 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. Open access under the Creative Commons Attribution 4.0 International (CC BY 4.0) licence | en_GB |
dc.subject | Peroxisomes | en_GB |
dc.subject | ER | en_GB |
dc.subject | ACBD5 | en_GB |
dc.subject | ACBD4 | en_GB |
dc.subject | VAPB | en_GB |
dc.subject | membrane contact sites | en_GB |
dc.subject | fatty acid metabolism | en_GB |
dc.title | Differential roles for ACBD4 and ACBD5 in peroxisome-ER interactions and lipid metabolism | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2023-07-05T14:57:52Z | |
dc.identifier.issn | 0021-9258 | |
exeter.article-number | 105013 | |
dc.description | This is the author accepted manuscript. The final version is available on open access from Elsevier via the DOI in this record | en_GB |
dc.description | Data availability: The research data supporting this publication are provided within this paper, or as supplementary information. | en_GB |
dc.identifier.eissn | 1083-351X | |
dc.identifier.journal | Journal of Biological Chemistry | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2023-06-29 | |
rioxxterms.version | AM | en_GB |
rioxxterms.licenseref.startdate | 2023-07-01 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2023-07-05T14:51:57Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2023-07-05T14:57:54Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2023-07-04 |
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Except where otherwise noted, this item's licence is described as © 2023 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. Open access under the Creative Commons Attribution 4.0 International (CC BY 4.0) licence