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FATP4 is the principal very long‐chain fatty acyl‐CoA synthetase in skin fibroblasts
Author(s) -
Jia Zhenzhen,
Moulson Casey L.,
Miner Jeffrey H.,
Watkins Paul A.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a607-c
Subject(s) - chemistry , biochemistry , fatty acid , western blot , peroxisome , lipid droplet , mitochondrion , organelle , gene
Fatty acid transport protein 4 (FATP4) is a fatty acyl‐CoA synthetase (ACS) that preferentially activates very long‐chain fatty acid (VLCFA) substrates, such as lignoceric acid (C24:0), to their CoA derivatives. To gain better insight into the physiological functions of FATP4, we established dermal fibroblast cell lines from FATP4‐deficient wrinkle‐free mice and w.t. mice. FATP4 −/− fibroblasts had no detectable FATP4 protein by Western blot. Compared to w.t. fibroblasts, cells lacking FATP4 had an 83% decrease in C24:0 activation. Peroxisomal degradation of C24:0 was reduced by 58%, and rates of C24:0 incorporation into major phospholipid species (54–64% decrease), triacylglycerol (64% decrease), and cholesterol esters (58% decrease) were significantly diminished. Because these lipid metabolic processes take place in different subcellular organelles, we used immunofluorescence and Western blotting of subcellular fractions to investigate the distribution of FATP4 protein, and measured enzyme activity in fractions from w.t. and FATP4 −/− fibroblasts. FATP4 protein and ACS activity localized to multiple organelles, including mitochondria, peroxisomes, ER, and the mitochondria‐associated membrane fraction. We conclude that in murine skin fibroblasts, FATP4 is the principal enzyme producing VLCFA‐CoA for major lipid metabolic pathways. Supported by NIH grants NS37355, HD10981, and AR49269.