title: Localization of a portion of the liver isoform of fatty-acid-binding protein (L-FABP) to peroxisomes.
abstract: The liver isoform of fatty-acid-binding protein (L-FABP) facilitates the cellular uptake, transport and metabolism of fatty acids and is also involved in the regulation of gene expressions and cell differentiation. Consistent with these functions, L-FABP is predominantly present in the cytoplasm and to a lesser extent in the nucleus; however, a significant portion of this protein has also been detected in fractions containing different organelles. More recent observations, notably on L-FABP-deficient mice, indicated a possible direct involvement of L-FABP in the peroxisomal oxidation of long-chain fatty acids. In order to clarify the links between L-FABP and peroxisomal lipid metabolism, we reinvestigated the subcellular distribution of the protein. Analytical subcellular fractionation by a method preserving the intactness of isolated peroxisomes, two-dimensional gel electrophoresis of peroxisomal matrix proteins combined with MS analysis, and immunoelectron microscopy of liver sections demonstrate the presence of L-FABP in the matrix of peroxisomes as a soluble protein. Peroxisomal L-FABP was highly inducible by clofibrate. The induction of L-FABP was accompanied by a marked increase in the binding capacity of peroxisomal matrix proteins for oleic acid and cis-parinaric acid. The peroxisomal beta-oxidation of palmitoyl-CoA and acyl-CoA thioesterase activity were stimulated by L-FABP, indicating that the protein modulates the function of peroxisomal lipid-metabolizing enzymes. The possible role of intraperoxisomal L-FABP in lipid metabolism is discussed.
authors.affiliation: Department of Biochemistry, Biocenter Oulu, University of Oulu, Linnanmaa, P.O. Box 3000, FIN-90014 Oulu, Finland. vasily.antonenkov@oulu.fi
authors.forename: Vasily D
authors.initials: VD
authors.lastname: Antonenkov
authors.forename: Raija T
authors.initials: RT
authors.lastname: Sormunen
authors.forename: Steffen
authors.initials: S
authors.lastname: Ohlmeier
authors.forename: Leen
authors.initials: L
authors.lastname: Amery
authors.forename: Marc
authors.initials: M
authors.lastname: Fransen
authors.forename: Guy P
authors.initials: GP
authors.lastname: Mannaerts
authors.forename: J Kalervo
authors.initials: JK
authors.lastname: Hiltunen
mesh_terms: D000818:Animals; D002994:Clofibrate / Q000494:pharmacology; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D020675:Peroxisomes / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C493321:Fabp1 protein, rat; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D020033:Protein Isoforms; D002994:Clofibrate