OGFOD1, a member of the 2-oxoglutarate and iron dependent dioxygenase family, functions in ischemic signaling

Ken Saito; Noritaka Adachi; Hideki Koyama; Masayuki Matsushita

doi:10.1016/j.febslet.2010.06.015

OGFOD1, a member of the 2-oxoglutarate and iron dependent dioxygenase family, functions in ischemic signaling

FEBS Lett. 2010 Aug 4;584(15):3340-7. doi: 10.1016/j.febslet.2010.06.015. Epub 2010 Jun 18.

Authors

Ken Saito¹, Noritaka Adachi, Hideki Koyama, Masayuki Matsushita

Affiliation

¹ Mitsubishi Kagaku Institute of Life Sciences (MITILS), 11 Minamiooya, Machida, Tokyo 194-8511, Japan.

PMID: 20579638
DOI: 10.1016/j.febslet.2010.06.015

Abstract

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.

MeSH terms

Amino Acid Sequence
Carrier Proteins / chemistry
Carrier Proteins / genetics
Carrier Proteins / metabolism*
Cell Death
Cell Nucleus / metabolism
Cell Survival / genetics
Dioxygenases / chemistry
Dioxygenases / genetics
Dioxygenases / metabolism*
Down-Regulation / genetics
Gene Knockdown Techniques
Gene Library
HeLa Cells
Humans
Iron / metabolism*
Ischemia / enzymology*
Ischemia / genetics
Ischemia / pathology
Ketoglutaric Acids / metabolism*
Mitochondrial Proton-Translocating ATPases / genetics
Mitochondrial Proton-Translocating ATPases / metabolism
Molecular Chaperones / genetics
Molecular Chaperones / metabolism
Molecular Sequence Data
Nuclear Proteins / chemistry
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
Protein Transport
RNA, Messenger / genetics
RNA, Messenger / metabolism
RNA, Small Interfering / metabolism
Signal Transduction*

Substances

Carrier Proteins
Ketoglutaric Acids
Molecular Chaperones
Nuclear Proteins
OGFOD1 protein, human
RNA, Messenger
RNA, Small Interfering
Iron
Dioxygenases
ATPAF1 protein, human
Mitochondrial Proton-Translocating ATPases