Document Detail

Regulation of cardiolipin biosynthesis by fatty acid transport protein-1 IN HEK 293 cells.
MedLine Citation:
PMID:  19523918     Owner:  NLM     Status:  MEDLINE    
Cardiolipin (CL) is a major phospholipid involved in energy metabolism mammalian mitochondria and fatty acid transport protein-1 (FATP-1) is a fatty acid transport protein that may regulate the intracellular level of fatty acyl-Coenzyme A's. Since fatty acids are required for oxidative phosphorylation via mitochondrial oxidation, we examined the effect of altering FATP-1 levels on CL biosynthesis. HEK-293 mock- and FATP-1 siRNA transfected cells or mock and FATP-1 expressing cells were incubated for 24 h with 0.1 mM oleic acid bound to albumin (1:1 molar ratio) then incubated for 24 h with 0.1 mM [1,3-(3)H]glycerol and radioactivity incorporated into CL determined. FATP-1 siRNA transfected cells exhibited reduced FATP-1 mRNA and increased incorporation of [1,3-(3)H]glycerol into CL (2-fold, p<0.05) compared to controls indicating elevation in de novo CL biosynthesis. The reason for this was an increase in [1,3-(3)H]glycerol uptake and increase in activity and mRNA expression of the CL biosynthetic enzymes. In contrast, expression of FATP-1 resulted a reduction in incorporation of [1,3-(3)H]glycerol into CL (65%, p<0.05) indicating reduced CL synthesis. [1,3-(3)H]Glycerol uptake was unaltered whereas activity of cytidine-5'-diphosphate-1,2-diacyl-sn-glycerol synthetase (CDS) and CDS-2 mRNA expression were reduced in FATP-1 expressing cells compared to control. In addition, in vitro CDS activity was reduced by exogenous addition of oleoyl-Coenzyme A. The data indicate that CL de novo biosynthesis may be regulated by FATP-1 through CDS-2 expression in HEK 293 cells.
Ryan W Mitchell; Grant M Hatch
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-06-11
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1788     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-05     Completed Date:  2009-12-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  2015-21     Citation Subset:  IM    
Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0T6.
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MeSH Terms
Acyl Coenzyme A / metabolism
Blotting, Western
Cardiolipins / biosynthesis*,  genetics
Cells, Cultured
Electrophoresis, Gel, Two-Dimensional
Fatty Acid Transport Proteins / antagonists & inhibitors,  genetics,  metabolism*
Fatty Acids / metabolism
Gene Expression Regulation*
Glycerol / metabolism
Kidney / cytology,  embryology
Mitochondria / metabolism
Phospholipids / metabolism
RNA, Messenger / genetics,  metabolism
RNA, Small Interfering / pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
//Canadian Institutes of Health Research
Reg. No./Substance:
0/Acyl Coenzyme A; 0/Cardiolipins; 0/Fatty Acid Transport Proteins; 0/Fatty Acids; 0/Phospholipids; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/SLC27A1 protein, human; 56-81-5/Glycerol

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