FEBS Letters
Volume 584, Issue 15 , Pages 3340-3347, 4 August 2010

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

Edited by Robert Barouki

  • Ken Saito

      Affiliations

    • Mitsubishi Kagaku Institute of Life Sciences (MITILS), 11 Minamiooya, Machida, Tokyo 194-8511, Japan
    • ,
  • Noritaka Adachi

      Affiliations

    • Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027, Japan
    • ,
  • Hideki Koyama

      Affiliations

    • Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027, Japan
    • ,
  • Masayuki Matsushita

      Affiliations

    • Mitsubishi Kagaku Institute of Life Sciences (MITILS), 11 Minamiooya, Machida, Tokyo 194-8511, Japan
    • Molecular and Cellular Physiology, University of the Ryukyus, Graduate School of Medicine, 207 Uehara, Nishihara, Okinawa 903-0215, Japan
    • Corresponding Author InformationCorresponding author. Address: Molecular and Cellular Physiology, University of the Ryukyus, Graduate School of Medicine, 207 Uehara, Nishihara, Okinawa 903-0215, Japan. Fax: +81 098 895 1402.

Received 26 February 2010; received in revised form 10 June 2010; accepted 11 June 2010. published online 18 June 2010.

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.

Keywords: Ischemia, Cell death, 2-Oxoglutarate and iron dependent dioxygenase

Abbreviations: 2-OG-Fe(II) dioxygenase, 2-oxoglutarate and iron dependent dioxygenase, PHD, prolyl hydroxylase, FIH, factor inhibiting HIF, OGD, oxygen and glucose deprivation, DMOG, dimethyloxalylglycine

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PII: S0014-5793(10)00505-3

doi:10.1016/j.febslet.2010.06.015

FEBS Letters
Volume 584, Issue 15 , Pages 3340-3347, 4 August 2010

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