DHRSX, also known as Dehydrogenase/reductase (SDR family) X-linked, is a gene with diverse functions. It is crucial for dolichol biosynthesis, a lipid essential for N-glycosylation as a carrier for activated sugars and nascent oligosaccharides. In this process, DHRSX catalyzes the first and third steps of converting polyprenol to dolichol, while SRD5A3 catalyzes the second step [1]. DHRSX also promotes starvation-induced autophagy and is secreted in a non-classical form [2].

In Lec5 and Lec9 Chinese hamster ovary cells, the absence of the DHRSX gene leads to N-glycosylation defects. These cells show increased levels of polyprenol and its derivatives, decreased levels of dolichol and derivatives, and lack the typical polyprenol dehydrogenase and dolichal reductase activities of DHRSX. Complementation with human DHRSX corrects N-glycan synthesis and polyisoprenoid level changes [3]. Whole-genome sequencing of these cells reveals that the genomic region containing DHRSX is absent, while SRD5A3 ORF has no mutations [3].

In summary, DHRSX is essential for dolichol biosynthesis and N-glycosylation. Its absence in cell models like Lec5 and Lec9 CHO cells clearly demonstrates its crucial role in these processes. Understanding DHRSX's function provides insights into the mechanisms of glycosylation-related disorders and autophagy regulation [1,2,3].

References:

1. Wilson, Matthew P, Kentache, Takfarinas, Althoff, Charlotte R, Foulquier, François, Bommer, Guido T. 2024. A pseudoautosomal glycosylation disorder prompts the revision of dolichol biosynthesis. In Cell, 187, 3585-3601.e22. doi:10.1016/j.cell.2024.04.041. https://pubmed.ncbi.nlm.nih.gov/38821050/

2. Zhang, Guoying, Luo, Yang, Li, Ge, Mo, Xiaoning, Wang, Lu. 2014. DHRSX, a novel non-classical secretory protein associated with starvation induced autophagy. In International journal of medical sciences, 11, 962-70. doi:10.7150/ijms.9529. https://pubmed.ncbi.nlm.nih.gov/25076851/

3. Kentache, Takfarinas, Althoff, Charlotte R, Caligiore, Francesco, Bommer, Guido T, Wilson, Matthew P. 2024. Absence of the dolichol synthesis gene DHRSX leads to N-glycosylation defects in Lec5 and Lec9 Chinese hamster ovary cells. In The Journal of biological chemistry, 300, 107875. doi:10.1016/j.jbc.2024.107875. https://pubmed.ncbi.nlm.nih.gov/39395802/