| First Author | Mori K | Year | 2023 |
| Journal | Mol Biol Cell | Volume | 34 |
| Issue | 9 | Pages | ar85 |
| PubMed ID | 37285239 | Mgi Jnum | J:341964 |
| Mgi Id | MGI:7542898 | Doi | 10.1091/mbc.E23-02-0042 |
| Citation | Mori K, et al. (2023) Role of 2-hydroxy acyl-CoA lyase HACL2 in odd-chain fatty acid production via alpha-oxidation in vivo. Mol Biol Cell 34(9):ar85 |
| abstractText | Although most fatty acids (FAs) are even chain, certain tissues, including brain, contain relatively large quantities of odd-chain FAs in their sphingolipids. One of the pathways producing odd-chain FAs is the alpha-oxidation of 2-hydroxy (2-OH) FAs, where 2-OH acyl-CoA lyases (HACL1 and HACL2) catalyze the key cleavage reaction. However, the contribution of each HACL to odd-chain FA production in vivo remains unknown. Here, we found that HACL2 and HACL1 play major roles in the alpha-oxidation of 2-OH FAs (especially very-long-chain types) and 3-methyl FAs (other alpha-oxidation substrates), respectively, using ectopic expression systems of human HACL2 and HACL1 in yeast and analyzing Hacl1 and/or Hacl2 knockout (KO) CHO-K1 cells. We then generated Hacl2 KO mice and measured the quantities of odd-chain and 2-OH lipids (free FAs and sphingolipids [ceramides, sphingomyelins, and monohexosylceramides]) in 17 tissues. We observed fewer odd-chain lipids and more 2-OH lipids in many tissues of Hacl2 KO mice than in wild-type mice, and of these differences the reductions were most prominent for odd-chain monohexosylceramides in the brain and ceramides in the stomach. These results indicate that HACL2-involved alpha-oxidation of 2-OH FAs is mainly responsible for odd-chain FA production in the brain and stomach. |
