title: Elevation of glutamine level by selenophosphate synthetase 1 knockdown induces megamitochondrial formation in Drosophila cells.
abstract: Although selenophosphate synthetase 1 (SPS1/SelD) is an essential gene in Drosophila, its function has not been determined. To elucidate its intracellular role, we targeted the removal of SPS1/SelD mRNA in Drosophila SL2 cells using RNA interference technology that led to the formation of vacuole-like globular structures. Surprisingly, these structures were identified as megamitochondria, and only depolarized mitochondria developed into megamitochondria. The mRNA levels of l(2)01810 and glutamine synthetase 1 (GS1) were increased by SPS1/SelD knockdown. Blocking the expression of GS1 and l(2)01810 completely inhibited the formation of megamitochondria induced by loss of SPS1/SelD activity and decreased the intracellular levels of glutamine to those of control cells suggesting that the elevated level of glutamine is responsible for megamitochondrial formation. Overexpression of GS1 and l(2)01810 had a synergistic effect on the induction of megamitochondrial formation and on the synthesis of glutamine suggesting that l(2)01810 is involved in glutamine synthesis presumably by activating GS1. Our results indicate that, in Drosophila, SPS1/SelD regulates the intracellular glutamine by inhibiting GS1 and l(2)01810 expression and that elevated levels of glutamine lead to a nutritional stress that provides a signal for megamitochondrial formation.
authors.affiliation: Laboratory of Molecular Genetics and Genomics, School of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742, Korea.
authors.forename: Myoung Sup
authors.initials: MS
authors.lastname: Shim
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Hee Kyoung
authors.initials: HK
authors.lastname: Jung
authors.forename: Kwang Hee
authors.initials: KH
authors.lastname: Lee
authors.forename: Xue-Ming
authors.initials: XM
authors.lastname: Xu
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Carlson
authors.forename: Ki Woo
authors.initials: KW
authors.lastname: Kim
authors.forename: Ick Young
authors.initials: IY
authors.lastname: Kim
authors.forename: Dolph L
authors.initials: DL
authors.lastname: Hatfield
authors.forename: Byeong Jae
authors.initials: BJ
authors.lastname: Lee
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D002460:Cell Line; D004330:Drosophila; D005973:Glutamine / Q000737:chemistry; D006801:Humans; D018613:Microscopy, Confocal / Q000379:methods; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism; D010641:Phenotype; D010770:Phosphotransferases / Q000235:genetics*; D034622:RNA Interference; D011994:Recombinant Proteins / Q000737:chemistry; D012643:Selenium / Q000378:metabolism; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D011994:Recombinant Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D005973:Glutamine; D000255:Adenosine Triphosphate; D010770:Phosphotransferases; C062762:selenophosphate synthetase; C022616:thiazolyl blue; D012643:Selenium