Localization of a portion of the liver isoform of fatty-acid-binding protein (L-FABP) to peroxisomes
Localization of a portion of the liver isoform of fatty-acid-binding protein (L-FABP) to peroxisomes
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DOI：
10.1042/bj20051058
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发表时间：
2006-03-01
影响因子：
4.1
通讯作者：
Hiltunen, JK
中科院分区：
文献类型：
--
作者：
Antonenkov, VD;Sormunen, RI;Hiltunen, JK
肝脏脂肪酸结合蛋白（L-FABP）促进细胞对脂肪酸的摄取、转运和代谢，并且还参与基因表达和细胞分化的调节。与这些功能相一致，L-FABP主要存在于细胞质中，在细胞核中的程度较小;然而，在含有不同细胞器的组分中也检测到该蛋白质的显著部分。最近的观察，特别是对L-FABP缺陷小鼠的观察，表明L-FABP可能直接参与长链脂肪酸的过氧化物酶体氧化。为了阐明L-FABP和过氧化物酶体脂质代谢之间的联系，我们重新研究了该蛋白的亚细胞分布。分析亚细胞分馏的方法保留完整的分离过氧化物酶体，二维凝胶电泳过氧化物酶体基质蛋白结合MS分析，和免疫电镜肝切片证明存在的L-脂肪酸结合蛋白的过氧化物酶体基质中，作为一种可溶性蛋白。过氧化物酶体L-FABP可被氯贝特高度诱导。L-FABP的诱导伴随着过氧化物酶体基质蛋白对油酸和顺式parinaric酸的结合能力的显着增加。棕榈酰辅酶A的过氧化物酶体β-氧化和酰基辅酶A硫酯酶活性被L-FABP刺激，表明该蛋白质调节过氧化物酶体脂质代谢酶的功能。过氧化物酶体内L-FABP在脂质代谢中的可能作用进行了讨论。
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.