ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis

Ohno, Yusuke; Suto, Shota; Yamanaka, Masao; Mizutani, Yukiko; Mitsutake, Susumu; Igarashi, Yasuyuki; Sassa, Takayuki; Kihara, Akio

ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis

Ohno, Yusuke; Suto, Shota; Yamanaka, Masao et al.

Proceedings of the National Academy of Sciences of the United States of America, 2010, 107(43), 18439-18444

Permalink : https://hdl.handle.net/2115/45300

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アクセス権	open access
URI	https://hdl.handle.net/2115/45300
タイトル	ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis
著者	Ohno, Yusuke ; Suto, Shota ; Yamanaka, Masao ; Mizutani, Yukiko ; Mitsutake, Susumu ; Igarashi, Yasuyuki ; Sassa, Takayuki ; Kihara, Akio
著者名 Ohno, Yusuke
著者名 Suto, Shota
著者名 Yamanaka, Masao
著者名 Mizutani, Yukiko
e-Rad_Researcher 10344475 著者名 Mitsutake, Susumu
e-Rad_Researcher 70091965 著者名 Igarashi, Yasuyuki
e-Rad_Researcher 20342793 著者名 Sassa, Takayuki
e-Rad_Researcher 50333620 著者名 Kihara, Akio
言語	英語
キーワード	acyl-CoA
	lipid metabolism
	monounsaturated fatty acid
	polyunsaturated fatty acid
	saturated fatty acid
発行日	2010-10-26
出版者	National Academy of Sciences
収録物名	Proceedings of the National Academy of Sciences of the United States of America
巻(号)	107(43)
ページ	18439-18444
抄録	Very long-chain fatty acids (VLCFAs) exert a variety of cellular functions and are associated with numerous diseases. However, the precise pathway behind their elongation has remained elusive. Moreover, few regulatory mechanisms for VLCFAs synthesis have been identified. Elongases catalyze the first of four steps in the VLCFA elongation cycle; mammals have seven elongases (ELOVL1-7). In the present study, we determined the precise substrate specificities of all the ELOVLs by in vitro analyses. Particularly notable was the high activity exhibited by ELOVL1 toward saturated and monounsaturated C20- and C22-CoAs, and that it was essential for the production of C24 sphingolipids, which are unique in their capacity to interdigitate within the membrane as a result of their long chain length. We further established that ELOVL1 activity is regulated with the ceramide synthase CERS2, an enzyme essential for C24 sphingolipid synthesis. This regulation may ensure that the production of C24-CoA by elongation is coordinated with its utilization. Finally, knock-down of ELOVL1 caused a reduction in the activity of the Src kinase LYN, confirming that C24-sphingolipids are particularly important in membrane microdomain function.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
PISSN	0027-8424
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1073/pnas.1005572107