Role of Elovl4 protein in the biosynthesis of docosahexaenoic acid.

The disk membranes of retinal photoreceptor outer segments and other neuronal and reproductive tissues are enriched in docosahexaenoic acid (DHA, 22:6n3), which is essential for their normal function and development. The fatty acid condensing enzyme Elongation of Very Long chain fatty acids-4 (ELOVL4) is highly expressed in retina photoreceptors as well as other tissues with high 22:6n3 content. Mutations in the ELOVL4 gene are associated with autosomal dominant Stargardt-like macular dystrophy (STGD3) and results in synthesis of a truncated protein that cannot be targeted to the endoplasmic reticulum (ER), the site of fatty acid biosynthesis. Considering the abundance and essential roles of 22:6n3 in ELOVL4-expressing tissues (except the skin), it was proposed that the ELOVL4 protein may be involved in 22:6n3 biosynthesis. We tested the hypothesis that the ELOVL4 protein is involved in 22:6n3 biosynthesis by selectively silencing expression of the protein in the cone photoreceptors derived cell line 661 w and showed that the ELOVL4 protein is not involved in DHA biosynthesis from the short chain fatty acid precursors 18:3n3 and 22:5n3.