OGFOD1, a member of the 2-oxoglutarate and iron dependent dioxygenase family, functions in ischemic signaling.
The 2-oxoglutarate and iron dependent dioxygenase family are crucial for cellular adaptation to changes in oxygen concentration. We found that cells with OGFOD1 gene silencing in this family showed resistance to cell death under ischemia, and cDNA microarray analysis of OGFOD1 knockout human cells revealed downregulation of ATPAF1. Although reintroduction of the OGFOD1 wild-type gene to OGFOD1 KO cells restored ATPAF1 mRNA levels, the catalytically inactive OGFOD1 mutants did not. Furthermore, introduction of ATPAF1 gene to OGFOD1 KO cells induced ischemic cell death. Thus, OGFOD1 plays an important role in ischemic cell survival and an OGFOD1 iron binding residue is required for ATPAF1 gene expression.
Saito
Ken
K
Mitsubishi Kagaku Institute of Life Sciences (MITILS), 11 Minamiooya, Machida, Tokyo 194-8511, Japan.
Adachi
Noritaka
N
Koyama
Hideki
H
Matsushita
Masayuki
M
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000235:genetics; D049308:Dioxygenases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D055785:Gene Knockdown Techniques; D015723:Gene Library; D006367:HeLa Cells; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007511:Ischemia / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D007656:Ketoglutaric Acids / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction
D002352:Carrier Proteins; D007656:Ketoglutaric Acids; D018832:Molecular Chaperones; D009687:Nuclear Proteins; C548916:OGFOD1 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D007501:Iron; D049308:Dioxygenases; C498318:ATPAF1 protein, human; D025261:Mitochondrial Proton-Translocating ATPases