Document Detail


Substrate specificity overlap and interaction between adrenoleukodystrophy protein (ALDP/ABCD1) and adrenoleukodystrophy-related protein (ALDRP/ABCD2).
MedLine Citation:
PMID:  21209459     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder caused by mutations in the ABCD1 gene, which encodes a peroxisomal member of the ATP-binding cassette (ABC) transporter subfamily D called ALDP. ALDP is supposed to function as a homodimer allowing the entry of CoA-esters of very-long chain fatty acids (VLCFA) into the peroxisome, the unique site of their β-oxidation. ALDP deficiency can be corrected by overexpression of ALDRP, its closest homolog. However, the exact nature of the substrates transported by ALDRP and its relationships with ALDP still remain unclear. To gain insight into the function of ALDRP, we used cell models allowing the induction in a dose-dependent manner of a wild type or a mutated non-functional ALDRP-EGFP fusion protein. We explored the consequences of the changes of ALDRP expression levels on the fatty acid content (saturated, monounsaturated, and polyunsaturated fatty acids) in phospholipids as well as on the levels of β-oxidation of 3 suspected substrates: C26:0, C24:0, and C22:6n-3 (DHA). We found an inverse correlation between the fatty acid content of saturated (C26:0, C24:0) and monounsaturated (C26:1, C24:1) VLCFA and the expression level of ALDRP. Interestingly, we obtained a transdominant-negative effect of the inactive ALDRP-EGFP on ALDP function. This effect is due to a physical interaction between ALDRP and ALDP that we evidenced by proximity ligation assays and coimmunoprecipitation. Finally, the β-oxidation assays demonstrate a role of ALDRP in the metabolism of saturated VLCFA (redundant with that of ALDP) but also a specific involvement of ALDRP in the metabolism of DHA.
Authors:
Emmanuelle C Genin; Flore Geillon; Catherine Gondcaille; Anne Athias; Philippe Gambert; Doriane Trompier; Stéphane Savary
Related Documents :
15208289 - Comparison of peg-modified albumin and hemoglobin in extreme hemodilution in the rat.
11480809 - Effect of an antibacterial varnish on lactic acid production in plaque adjacent to fixe...
3522109 - Manganese: its acquisition by and function in the lactic acid bacteria.
3083699 - Amelioration of hypoxia-induced lactic acidosis by superimposed hypercapnea or hydrochl...
17002469 - Tartaric acid recovery from distilled lees and use of the residual solid as an economic...
21483909 - Direct synthesis of bifunctional periodic mesoporous benzene-silicas functionalized wit...
1369419 - An integrated process for the production and biotransformation of penicillin.
17477309 - Dietary fish oil as hepatoprotective agent in mus musculus.
11403489 - Evaluation of the lipophilicity of bile acids and their derivatives by thin-layer chrom...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-01-05
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-10     Completed Date:  2011-05-11     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8075-84     Citation Subset:  IM    
Affiliation:
INSERM, UMR866, Centre de Recherche Lipides, Nutrition, Cancer, Dijon F-21000, France.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / genetics,  metabolism*
Adrenoleukodystrophy / genetics,  metabolism
Animals
Cell Line, Tumor
Fatty Acids / genetics,  metabolism*
Oxidation-Reduction
Peroxisomes / enzymology*,  genetics
Rats
Chemical
Reg. No./Substance:
0/Abcd2 protein, rat; 0/Fatty Acids
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Korea's National Health Insurance--lessons from the past three decades.
Next Document:  Ubiquitin-dependent proteasomal degradation of human liver cytochrome P450 2E1: identification of si...