Acyl/alkyl-glycerone phosphate reductase DHRS7 is involved in the production of distinct plasmalogen species from DHRS7B

Plasmalogens are ether lipids that constitute mammalian membranes. In their biosynthetic pathway, DHRS7B functions as an alkylglycerone phosphate reductase. Here we investigated whether DHRS7, which shares high sequence similarity with DHRS7B, also contributes to plasmalogen production. We generated DHRS7 and DHRS7B knockout (KO) cells, as well as double KO cells, and quantified ethanolamine plasmalogens (PEPs). DHRS7 and DHRS7B were involved in the production of distinct fatty acid species: in the de novo synthesis pathway, DHRS7 contributed most strongly to the synthesis of C18:1 species, followed by C16:0 and C22:4 species, whereas DHRS7B contributed to the synthesis of all species examined. These differences in contribution in the de novo pathway resulted in further differences in the steady-state composition of PEPs. DHRS7 and DHRS7B also showed different intracellular localization: endoplasmic reticulum for DHRS7 and peroxisomes for DHRS7B. In vitro, DHRS7 exhibited both alkylglycerone and acylglycerone phosphate reductase activities, similarly to DHRS7B. Collectively, our findings indicate that DHRS7 is a novel alkyl/acylglycerone phosphate reductase that differs from DHRS7B in both subcellular localization and the profile of plasmalogen species produced.