Prolyl-hydroxylase PHD3 interacts with pyruvate dehydrogenase (PDH)-E1β and regulates the cellular PDH activity

Daisuke Kikuchi, Yoji Andrew Minamishima, Koh Nakayama

研究成果: Article

14 引用 (Scopus)

抄録

Cells are frequently exposed to hypoxia in physiological and pathophysiological conditions in organisms. Control of energy metabolism is one of the critical functions of the hypoxic response. Hypoxia-Inducible Factor (HIF) is a central transcription factor that regulates the hypoxic response. HIF prolyl-hydroxylase PHDs are the enzymes that hydroxylate the α subunit of HIF and negatively regulate its expression. To further understand the physiological role of PHD3, proteomics were used to identify PHD3-interacting proteins, and pyruvate dehydrogenase (PDH)-E1β was identified as such a protein. PDH catalyzes the conversion of pyruvate to acetyl-coA, thus playing a key role in cellular energy metabolism. PDH activity was significantly decreased in PHD3-depleted MCF7 breast cancer cells and PHD3-/- MEFs. PHD3 depletion did not affect the expression of the PDH-E1α, E1β, and E2 subunits, or the phosphorylation status of E1α, but destabilized the PDH complex (PDC), resulting in less functional PDC. Finally, PHD3-/- cells were resistant to cell death in prolonged hypoxia with decreased production of ROS. Taken together, the study reveals that PHD3 regulates PDH activity in cells by physically interacting with PDC.

元の言語English
ページ(範囲)288-294
ページ数7
ジャーナルBiochemical and Biophysical Research Communications
451
発行部数2
DOI
出版物ステータスPublished - 2014 8 22

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Pyruvate Dehydrogenase (Lipoamide)
Prolyl Hydroxylases
Pyruvic Acid
Oxidoreductases
Energy Metabolism
Pyruvate Dehydrogenase Complex
Phosphorylation
Cell death
Proteins
Transcription Factors
Proteomics
Cells
Cell Death
Hypoxia
Breast Neoplasms
Enzymes

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

これを引用

Prolyl-hydroxylase PHD3 interacts with pyruvate dehydrogenase (PDH)-E1β and regulates the cellular PDH activity. / Kikuchi, Daisuke; Minamishima, Yoji Andrew; Nakayama, Koh.

:: Biochemical and Biophysical Research Communications, 巻 451, 番号 2, 22.08.2014, p. 288-294.

研究成果: Article

Kikuchi, Daisuke ; Minamishima, Yoji Andrew ; Nakayama, Koh. / Prolyl-hydroxylase PHD3 interacts with pyruvate dehydrogenase (PDH)-E1β and regulates the cellular PDH activity. :: Biochemical and Biophysical Research Communications. 2014 ; 巻 451, 番号 2. pp. 288-294.
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