Peroxisomal fatty acid uptake mechanism in Saccharomyces cerevisiae.

C.W.T. van Roermund, L. Ijlst, W. Majczak, H.R. Waterham, H. Folkerts, R.J.A. Wanders, K.J. Hellingwerf

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Abstract

Peroxisomes play a major role in human cellular lipid metabolism, including fatty acid beta-oxidation. The most frequent peroxisomal disorder is X-linked adrenoleukodystrophy, which is caused by mutations in ABCD1. The biochemical hallmark of X-linked adrenoleukodystrophy is the accumulation of very long chain fatty acids (VLCFAs) due to impaired peroxisomal beta-oxidation. Although this suggests a role of ABCD1 in VLCFA import into peroxisomes, no direct experimental evidence is available to substantiate this. To unravel the mechanism of peroxisomal VLCFA transport, we use Saccharomyces cerevisiae as a model organism. Here we provide evidence that in this organism very long chain acyl-CoA esters are hydrolyzed by the Pxa1p-Pxa2p complex prior to the actual transport of their fatty acid moiety into the peroxisomes with the CoA presumably being released into the cytoplasm. The Pxa1p-Pxa2p complex functionally interacts with the acyl-CoA synthetases Faa2p and/or Fat1p on the inner surface of the peroxisomal membrane for subsequent re-esterification of the VLCFAs. Importantly, the Pxa1p-Pxa2p complex shares this molecular mechanism with HsABCD1 and HsABCD2.
Original languageEnglish
Pages (from-to)20144-20153
JournalThe Journal of Biological Chemistry
Volume287
Issue number24
DOIs
Publication statusPublished - 2012

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