Retinol dehydrogenase 11 is essential for the maintenance of retinol homeostasis in liver and testis in mice

• Published in: The Journal of biological chemistry 2018-05, Vol.293 (18), p.6996-7007
• Main Authors: Belyaeva, Olga V., Wu, Lizhi, Shmarakov, Igor, Nelson, Peter S., Kedishvili, Natalia Y.
• Format: Article
• Language: English
• Subjects: Animals; beta Carotene - administration & dosage; beta Carotene - metabolism; carotenoid; dehydrogenase; Diet; Female; Gene Expression; Homeostasis; Male; Metabolism; Mice; Mice, Knockout; Microsomes - metabolism; Microsomes, Liver - metabolism; Oxidoreductases - genetics; Oxidoreductases - metabolism; reductase; retinaldehyde; Retinaldehyde - metabolism; retinoic acid; retinol; Retinol-Binding Proteins, Plasma - metabolism; Signal Transduction; Testis - metabolism; vitamin A; Vitamin A - metabolism; Vitamin A Deficiency - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.RA117.001646

Retinol dehydrogenase 11 (RDH11) is a microsomal short-chain dehydrogenase/reductase that recognizes all-trans– and cis–retinoids as substrates and prefers NADPH as a cofactor. Previous work has suggested that RDH11 contributes to the oxidation of 11-cis–retinol to 11-cis–retinaldehyde during the visual cycle in the eye's retinal pigment epithelium. However, the role of RDH11 in metabolism of all-trans–retinoids remains obscure. Here, we report that microsomes isolated from the testes and livers of Rdh11−/− mice fed a regular diet exhibited a 3- and 1.7-fold lower rate of all-trans–retinaldehyde conversion to all-trans–retinol, respectively, than the microsomes of WT littermates. Testes and livers of Rdh11−/− mice fed a vitamin A–deficient diet had ∼35% lower levels of all-trans–retinol than those of WT mice. Furthermore, the conversion of β-carotene to retinol via retinaldehyde as an intermediate appeared to be impaired in the testes of Rdh11−/−/retinol-binding protein 4−/−(Rbp4−/−) mice, which lack circulating holo RBP4 and rely on dietary supplementation with β-carotene for maintenance of their retinoid stores. Together, these results indicate that in mouse testis and liver, RDH11 functions as an all-trans–retinaldehyde reductase essential for the maintenance of physiological levels of all-trans–retinol under reduced vitamin A availability.