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ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis
Open accessAbstract
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, knockdown of ELOVL1 caused a reduction in the activity of the Src kinase LYN, confirming that C24-sphingolipids are particularly important in membrane microdomain function.
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“The 22-carbon lipid AdA, a product of AA elongation (Jump, 2009; Ohno et al., 2010) and precursor of dihomo prostaglandins (Sprecher et al., 1982), also increased in senescent cells (Figure 1B).”
From Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis (2021) · cites this paper as Ohno et al., 2010
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Metadata
- Authors
- Ohno, Y., Suto, S., Yamanaka, M., Mizutani, Y., Mitsutake, S., Igarashi, Y., Sassa, T., & Kihara, A.
- Affiliations
- Hokkaido University (JP)
- Corresponding author
- Ohno, Yusuke
- Suto, Shota
- Kihara, Akio
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-10-11
- Volume
- 107
- Issue
- 43
- Pages
- 18439-18444
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2973002
- OpenAlex
- W2014581910
- Cited by
- 382
- References
- 34
- Citations by year
- 2026: 15 · 2025: 20 · 2024: 21 · 2023: 32 · 2022: 32 · 2021: 58 · 2020: 24 · 2019: 28 · 2018: 26 · 2017: 25 · 2016: 18 · 2015: 18 · 2014: 19 · 2013: 19 · 2012: 16
- FWCI
- 5.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Hokkaido University Collection of Scholarly and Academic Papers (Hokkaido University) (submittedVersion)
- Funders
- Ono Medical Research Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- ELOVL1, very long chain fatty acids, fatty acid elongation, substrate specificity, ceramide synthase 2, ceramide synthase, Lyn kinase, lipid rafts
- MeSH terms
- Fatty Acid Elongases, Acetyltransferases, Acyl Coenzyme A, Base Sequence, Cell Line, Fatty Acids, Female, HeLa Cells, Humans, Male, Membrane Proteins, Recombinant Proteins, RNA, Messenger, Saccharomyces cerevisiae, Sphingolipids, Substrate Specificity, Tissue Distribution, DNA Primers, Membrane Microdomains, Tumor Suppressor Proteins, RNA, Small Interfering, Sphingosine N-Acyltransferase, Gene Knockdown Techniques, In Vitro Techniques
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