Drosophila selenophosphate synthetase 1 regulates vitamin B6 metabolism: prediction and confirmation
- Equal contributors
1 Department of Biological Sciences, Seoul National University, Seoul 151-742, Korea
2 Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 151-742, Korea
3 Department of Statistics, Seoul National University, Seoul 151-742, Korea
4 Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
5 Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA
BMC Genomics 2011, 12:426 doi:10.1186/1471-2164-12-426Published: 24 August 2011
There are two selenophosphate synthetases (SPSs) in higher eukaryotes, SPS1 and SPS2. Of these two isotypes, only SPS2 catalyzes selenophosphate synthesis. Although SPS1 does not contain selenophosphate synthesis activity, it was found to be essential for cell growth and embryogenesis in Drosophila. The function of SPS1, however, has not been elucidated.
Differentially expressed genes in Drosophila SL2 cells were identified using two-way analysis of variance methods and clustered according to their temporal expression pattern. Gene ontology analysis was performed against differentially expressed genes and gene ontology terms related to vitamin B6 biosynthesis were found to be significantly affected at the early stage at which megamitochondria were not formed (day 3) after SPS1 knockdown. Interestingly, genes related to defense and amino acid metabolism were affected at a later stage (day 5) following knockdown. Levels of pyridoxal phosphate, an active form of vitamin B6, were decreased by SPS1 knockdown. Treatment of SL2 cells with an inhibitor of pyridoxal phosphate synthesis resulted in both a similar pattern of expression as that found by SPS1 knockdown and the formation of megamitochondria, the major phenotypic change observed by SPS1 knockdown.
These results indicate that SPS1 regulates vitamin B6 synthesis, which in turn impacts various cellular systems such as amino acid metabolism, defense and other important metabolic activities.