RRC ID 62787
著者 Narita T, Naganuma T, Sase Y, Kihara A.
タイトル Long-chain bases of sphingolipids are transported into cells via the acyl-CoA synthetases.
ジャーナル Sci Rep
Abstract Transport of dietary lipids into small-intestinal epithelial cells is pathologically and nutritionally important. However, lipid uptake remains an almost unexplored research area. Although we know that long-chain bases (LCBs), constituents of sphingolipids, can enter into cells efficiently, the molecular mechanism of LCB uptake is completely unclear. Here, we found that the yeast acyl-CoA synthetases (ACSs) Faa1 and Faa4 are redundantly involved in LCB uptake. In addition to fatty acid-activating activity, transporter activity toward long-chain fatty acids (LCFAs) has been suggested for ACSs. Both LCB and LCFA transports were largely impaired in faa1Δ faa4Δ cells. Furthermore, LCB and LCFA uptakes were mutually competitive. However, the energy dependency was different for their transports. Sodium azide/2-deoxy-D-glucose treatment inhibited import of LCFA but not that of LCB. Furthermore, the ATP-AMP motif mutation FAA1 S271A largely impaired the metabolic activity and LCFA uptake, while leaving LCB import unaffected. These results indicate that only LCFA transport requires ATP. Since ACSs do not metabolize LCBs as substrates, Faa1 and Faa4 are likely directly involved in LCB transport. Furthermore, we revealed that ACSs are also involved in LCB transport in mammalian cells. Thus, our findings provide strong support for the hypothesis that ACSs directly transport LCFAs.
巻・号 6
ページ 25469
公開日 2016-5-3
DOI 10.1038/srep25469
PII srep25469
PMID 27136724
PMC PMC4853782
MeSH Acyl Coenzyme A / genetics Acyl Coenzyme A / metabolism* Animals Biological Transport / genetics Coenzyme A Ligases / genetics Coenzyme A Ligases / metabolism* Fatty Acids / genetics Fatty Acids / metabolism Lipid Metabolism / genetics Lipids Rats Saccharomyces cerevisiae / genetics Saccharomyces cerevisiae Proteins / genetics Saccharomyces cerevisiae Proteins / metabolism* Sphingolipids / genetics Sphingolipids / metabolism*
IF 3.998
リソース情報
ヒト・動物細胞 IEC 6(RCB0993)