University of Oulu

Ala-Nisula, T., Sah-Teli, S.K., Ronkainen, V.-P., Dimova, E.Y. and Koivunen, P. (2023), Human phytanoyl-CoA dioxygenase domain-containing 1 (PHYHD1) is a putative oxygen sensor associated with RNA and carbohydrate metabolism. FEBS Lett, 597: 1651-1666.

Human phytanoyl-CoA dioxygenase domain-containing 1 (PHYHD1) is a putative oxygen sensor associated with RNA and carbohydrate metabolism

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Author: Ala-Nisula, Tuulia1; Sah-Teli, Shiv K.1; Ronkainen, Veli-Pekka2;
Organizations: 1Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, Oulu Center for Cell-Matrix Research, University of Oulu, Finland
2Biocenter Oulu, University of Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.3 MB)
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Language: English
Published: John Wiley & Sons, 2023
Publish Date: 2023-09-13


Human phytanoyl-CoA dioxygenase domain-containing 1 (PHYHD1) is a 2-oxoglutarate (2OG)-dependent dioxygenase implicated in Alzheimer’s disease, some cancers, and immune cell functions. The substrate, kinetic and inhibitory properties, function and subcellular localization of PHYHD1 are unknown. We used recombinant expression and enzymatic, biochemical, biophysical, cellular and microscopic assays for their determination. The apparent Km values of PHYHD1 for 2OG, Fe²⁺ and O₂ were 27, 6 and > 200 μm, respectively. PHYHD1 activity was tested in the presence of 2OG analogues, and it was found to be inhibited by succinate and fumarate but not R-2-hydroxyglutarate, whereas citrate acted as an allosteric activator. PHYHD1 bound mRNA, but its catalytic activity was inhibited upon interaction. PHYHD1 was found both in the nucleus and cytoplasm. Interactome analyses linked PHYHD1 to cell division and RNA metabolism, while phenotype analyses linked it to carbohydrate metabolism. Thus, PHYHD1 is a potential novel oxygen sensor regulated by mRNA and citrate.

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Series: FEBS letters
ISSN: 0014-5793
ISSN-E: 1873-3468
ISSN-L: 0014-5793
Volume: 597
Issue: 12
Pages: 1651 - 1666
DOI: 10.1002/1873-3468.14666
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This work was supported by grants from the Academy of Finland (308009, 339900), the S. Jusélius Foundation, the Jane and Aatos Erkko Foundation and the Finnish Cancer Organizations to PK.
Academy of Finland Grant Number: 308009
Detailed Information: 308009 (Academy of Finland Funding decision)
339900 (Academy of Finland Funding decision)
Copyright information: © 2023 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.