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ALDH1L2 is the mitochondrial homolog of 10-formyltetrahydrofolate dehydrogenase.

Publication ,  Journal Article
Krupenko, NI; Dubard, ME; Strickland, KC; Moxley, KM; Oleinik, NV; Krupenko, SA
Published in: J Biol Chem
July 23, 2010

Cytosolic 10-formyltetrahydrofolate dehydrogenase (FDH, ALDH1L1) is an abundant enzyme of folate metabolism. It converts 10-formyltetrahydrofolate to tetrahydrofolate and CO(2) in an NADP(+)-dependent reaction. We have identified a gene at chromosome locus 12q24.11 of the human genome, the product of which has 74% sequence similarity with cytosolic FDH. This protein has an extra N-terminal sequence of 22 amino acid residues, predicted to be a mitochondrial translocation signal. Transfection of COS-7 or A549 cell lines with a construct in which green fluorescent protein was introduced between the leader sequence and the rest of the putative mitochondrial FDH (mtFDH) has demonstrated mitochondrial localization of the fusion protein, suggesting that the identified gene encodes a mitochondrial enzyme. Purified pig liver mtFDH displayed dehydrogenase/hydrolase activities similar to cytosolic FDH. Real-time PCR performed on an array of human tissues has shown that although cytosolic FDH mRNA is highest in liver, kidney, and pancreas, mtFDH mRNA is most highly expressed in pancreas, heart, and brain. In contrast to the cytosolic enzyme, which is not detectable in cancer cells, the presence of mtFDH was demonstrated in several human cancer cell lines by conventional and real-time PCR and by Western blot. Analysis of genomes of different species indicates that the mitochondrial enzyme is a later evolutionary product when compared with the cytosolic enzyme. We propose that this novel mitochondrial enzyme is a likely source of CO(2) production from 10-formyltetrahydrofolate in mitochondria and plays an essential role in the distribution of one-carbon groups between the cytosolic and mitochondrial compartments of the cell.

Duke Scholars

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

July 23, 2010

Volume

285

Issue

30

Start / End Page

23056 / 23063

Location

United States

Related Subject Headings

  • Swine
  • Sequence Homology, Amino Acid
  • Sequence Alignment
  • Rats
  • Protein Transport
  • Oxidoreductases Acting on CH-NH Group Donors
  • Molecular Sequence Data
  • Mitochondria
  • Mice
  • Humans
 

Citation

APA
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ICMJE
MLA
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Krupenko, N. I., Dubard, M. E., Strickland, K. C., Moxley, K. M., Oleinik, N. V., & Krupenko, S. A. (2010). ALDH1L2 is the mitochondrial homolog of 10-formyltetrahydrofolate dehydrogenase. J Biol Chem, 285(30), 23056–23063. https://doi.org/10.1074/jbc.M110.128843
Krupenko, Natalia I., Marianne E. Dubard, Kyle C. Strickland, Kelly M. Moxley, Natalia V. Oleinik, and Sergey A. Krupenko. “ALDH1L2 is the mitochondrial homolog of 10-formyltetrahydrofolate dehydrogenase.J Biol Chem 285, no. 30 (July 23, 2010): 23056–63. https://doi.org/10.1074/jbc.M110.128843.
Krupenko NI, Dubard ME, Strickland KC, Moxley KM, Oleinik NV, Krupenko SA. ALDH1L2 is the mitochondrial homolog of 10-formyltetrahydrofolate dehydrogenase. J Biol Chem. 2010 Jul 23;285(30):23056–63.
Krupenko, Natalia I., et al. “ALDH1L2 is the mitochondrial homolog of 10-formyltetrahydrofolate dehydrogenase.J Biol Chem, vol. 285, no. 30, July 2010, pp. 23056–63. Pubmed, doi:10.1074/jbc.M110.128843.
Krupenko NI, Dubard ME, Strickland KC, Moxley KM, Oleinik NV, Krupenko SA. ALDH1L2 is the mitochondrial homolog of 10-formyltetrahydrofolate dehydrogenase. J Biol Chem. 2010 Jul 23;285(30):23056–23063.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

July 23, 2010

Volume

285

Issue

30

Start / End Page

23056 / 23063

Location

United States

Related Subject Headings

  • Swine
  • Sequence Homology, Amino Acid
  • Sequence Alignment
  • Rats
  • Protein Transport
  • Oxidoreductases Acting on CH-NH Group Donors
  • Molecular Sequence Data
  • Mitochondria
  • Mice
  • Humans