NDLI: Deficiency of a Retinal Dystrophy Protein, Acyl-CoA Binding Domain-containing 5 (ACBD5), Impairs Peroxisomal β-Oxidation of Very-long-chain Fatty Acids

Please wait, while we are loading the content...

Deficiency of a Retinal Dystrophy Protein, Acyl-CoA Binding Domain-containing 5 (ACBD5), Impairs Peroxisomal β-Oxidation of Very-long-chain Fatty Acids

Content Provider	Scilit
Author	Yagita, Yuichi Shinohara, Kyoko Abe, Yuichi Nakagawa, Keiko Al-Owain, Mohammed Alkuraya, Fowzan S. Fujiki, Yukio
Copyright Year	2017
Description	Journal: Journal of Biological Chemistry Acyl-CoA binding domain-containing 5 (ACBD5) is a peroxisomal protein that carries an acyl-CoA binding domain (ACBD) at its N-terminal region. The recent identification of a mutation in the ACBD5 gene in patients with a syndromic form of retinal dystrophy highlights the physiological importance of ACBD5 in humans. However, the underlying pathogenic mechanisms and the precise function of ACBD5 remain unclear. We herein report that ACBD5 is a peroxisomal tail-anchored membrane protein exposing its ACBD to the cytosol. Using patient-derived fibroblasts and ACBD5 knock-out HeLa cells generated via genome editing, we demonstrate that ACBD5 deficiency causes a moderate but significant defect in peroxisomal β-oxidation of very-long-chain fatty acids (VLCFAs) and elevates the level of cellular phospholipids containing VLCFAs without affecting peroxisome biogenesis, including the import of membrane and matrix proteins. Both the N-terminal ACBD and peroxisomal localization of ACBD5 are prerequisite for efficient VLCFA β-oxidation in peroxisomes. Furthermore, ACBD5 preferentially binds very-long-chain fatty acyl-CoAs (VLC-CoAs). Together, these results suggest a direct role of ACBD5 in peroxisomal VLCFA β-oxidation. Based on our findings, we propose that ACBD5 captures VLC-CoAs on the cytosolic side of the peroxisomal membrane so that the transport of VLC-CoAs into peroxisomes and subsequent β-oxidation thereof can proceed efficiently. Our study reclassifies ACBD5-related phenotype as a novel peroxisomal disorder.
Related Links	http://www.jbc.org/content/292/2/691.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241743/pdf http://www.jbc.org/article/S0021925820401991/pdf
Ending Page	705
Page Count	15
Starting Page	691
ISSN	00219258
e-ISSN	1083351X
DOI	10.1074/jbc.m116.760090
Journal	Journal of Biological Chemistry
Issue Number	2
Volume Number	292
Language	English
Publisher	Elsevier BV
Publisher Date	2017-01-01
Access Restriction	Open
Subject Keyword	Journal: Journal of Biological Chemistry Biochemistry and Molecular Biology Acyl-coa-binding Protein Fatty Acid Β-oxidation Genetic Disease Lipid Metabolism Neurological Disease Retinal Degeneration Retinal Dystrophy
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Deficiency of a Retinal Dystrophy Protein, Acyl-CoA Binding Domain-containing 5 (ACBD5), Impairs Peroxisomal β-Oxidation of Very-long-chain Fatty Acids

Peroxisomal fatty acid β-oxidation in human skin fibroblasts: X-linked adrenoleukodystrophy, a peroxisomal very long chain fatty acyl-CoA synthetase deficiency?

Strategies for Correcting Very Long Chain Acyl-CoA Dehydrogenase Deficiency

Regulation of very-long acyl chain ceramide synthesis by acyl-CoA-binding protein

Regulation of very-long acyl chain ceramide synthesis by acyl-CoA-binding protein

High-affinity binding of very-long-chain fatty acyl-CoA esters to the peroxisomal non-specific lipid-transfer protein (sterol carrier protein-2).

A Novel Homozygous <i>ACBD5</i> Variant in an Emerging Peroxisomal Disorder Presenting with Retinal Dystrophy and a Review of the Literature.

Peroxisomal and Mitochondrial Fatty Acid β-Oxidation in Mice Nullizygous for Both Peroxisome Proliferator-activated Receptor α and Peroxisomal Fatty Acyl-CoA Oxidase GENOTYPE CORRELATION WITH FATTY LIVER PHENOTYPE

Tissue-Specific Strategies of the Very-Long Chain Acyl-CoA Dehydrogenase-Deficient (VLCAD−/−) Mouse to Compensate a Defective Fatty Acid β-Oxidation

Deficiency of a Retinal Dystrophy Protein, Acyl-CoA Binding Domain-containing 5 (ACBD5), Impairs Peroxisomal β-Oxidation of Very-long-chain Fatty Acids

Similar Documents

Deficiency of a Retinal Dystrophy Protein, Acyl-CoA Binding Domain-containing 5 (ACBD5), Impairs Peroxisomal β-Oxidation of Very-long-chain Fatty Acids

Peroxisomal fatty acid β-oxidation in human skin fibroblasts: X-linked adrenoleukodystrophy, a peroxisomal very long chain fatty acyl-CoA synthetase deficiency?

Strategies for Correcting Very Long Chain Acyl-CoA Dehydrogenase Deficiency

Regulation of very-long acyl chain ceramide synthesis by acyl-CoA-binding protein

Regulation of very-long acyl chain ceramide synthesis by acyl-CoA-binding protein

High-affinity binding of very-long-chain fatty acyl-CoA esters to the peroxisomal non-specific lipid-transfer protein (sterol carrier protein-2).

A Novel Homozygous <i>ACBD5</i> Variant in an Emerging Peroxisomal Disorder Presenting with Retinal Dystrophy and a Review of the Literature.

Peroxisomal and Mitochondrial Fatty Acid β-Oxidation in Mice Nullizygous for Both Peroxisome Proliferator-activated Receptor α and Peroxisomal Fatty Acyl-CoA Oxidase GENOTYPE CORRELATION WITH FATTY LIVER PHENOTYPE

Tissue-Specific Strategies of the Very-Long Chain Acyl-CoA Dehydrogenase-Deficient (VLCAD−/−) Mouse to Compensate a Defective Fatty Acid β-Oxidation

Deficiency of a Retinal Dystrophy Protein, Acyl-CoA Binding Domain-containing 5 (ACBD5), Impairs Peroxisomal β-Oxidation of Very-long-chain Fatty Acids