Skip to content
DraconiticResearch
Search Sources API
193,349 studies31 sourcesUpdated 23 min ago
Peer-reviewedCC BY 4.0Cells

Genetic Variations in the Folate Regulatory Enzyme ALDH1L1: Impact on Cell Metabolism, Proliferation, and Motility

  • Halle M. Meyers1,2
  • Amira A. Abdellatef1
  • Natalia I. Krupenko1,2
  • Baba Mass1
  • Venkata Saroja Voruganti1,2
  • Susan Sumner1,2
  • Blake R. Rushing1,2
  • Sergey A. Krupenko1,2
  1. 1Nutrition Research Institute, UNC–Chapel Hill, Kannapolis, NC 28081, USA
  2. 2Department of Nutrition, UNC–Chapel Hill, Chapel Hill, NC 27599, USA
Open at sourceDOICite

Abstract

In humans, six common non-synonymous exonic single-nucleotide polymorphisms in ALDH1L1 lead to ten enzyme haplotypes. Since ALDH1L1 is a metabolic regulator and a candidate tumor suppressor, we studied how haplotype variants affect metabotypes, proliferation and motility. Using lentiviral delivery to A549 and PC3 cells, we have generated two cell panels, with each cell line in the panel carrying one of ten ALDH1L1 haplotype variants. Untargeted metabolomics revealed strong differences in metabotypes between cells carrying ALDH1L1 variants. Certain ALDH1L1 variants had decreased ability to regulate one-carbon metabolism and downstream pathways, including amino acid and glutathione metabolism, nucleotide biosynthesis, and the TCA cycle. The direct comparison of A549 and PC3 cells using an untargeted metabolomic dataset also showed that the two cell lines have vastly different metabotypes. In agreement with this finding, the analysis of A549 and PC3 ALDH1L1 haplotype panels suggested that the ALDH1L1-linked metabolic regulation is strongly influenced by specific cellular metabotypes and genetic background. ALDH1L1 variants also exhibited reduced inhibition of cellular proliferation and motility compared to the most common haplotype, which supports further investigation of their potential relevance to individual risk of metabolic disorders.

Related

  1. A transcriptome map reveals conserved and lineage-specific sRNAs that regulate motility and metabolism across Vibrio
    Z. Jia, H. Zhang, D. Falush +2
    bioRxivPreprintCC BYFull textMicrobiologybioRxiv
  2. Cross-regulatory sRNA networks shape adaptive stress responses in Staphylococcus aureus: RsaC and RsaOI regulate galactose metabolism and cell wall homeostasis
    H. ROBIN, M. GERMAIN, C. SILARD +4
    bioRxivPreprintAll rights reservedFull textMicrobiologybioRxiv
  3. Genetic Insights into the Comorbidity of Congenital Heart Disease and Neurodevelopmental Disorders: Focus on Copy Number Variations.
    Ziyi Ye, Yingzhong He, Jing Guo +4
    Journal of cardiovascular development and diseasePeer-reviewedCC BYFull textGenetics & genomicsEurope PMC
  4. Wolbachia outcompetes mosquito-borne viruses by reprogramming host ATPSβ1-driven ATP metabolism toward symbiotic proliferation
    Hao Yuan, Yalan Zhang, Yaqi Zhao +13
    PLOS PathogensPeer-reviewedCC BY 4.0Full textMolecular biology & gene regulationMicrobiologyPLOSPMC
  5. Genetic Relationships, Whole-Fruit Oil Variations, and Quantitative Trait Diversity in Elite Symplocos paniculata Accessions from Hunan Revealed by GBS.
    Jiating Zhao, Beilei Xie, Lijuan Jiang +8
    BiologyPeer-reviewedCC BYFull textGenetics & genomicsEurope PMC

Cite

BibTeXRIS
BibTeX
@article{meyers2026genetic,
  title = {{Genetic Variations in the Folate Regulatory Enzyme ALDH1L1: Impact on Cell Metabolism, Proliferation, and Motility}},
  author = {Halle M. Meyers and Amira A. Abdellatef and Natalia I. Krupenko and Baba Mass and Venkata Saroja Voruganti and Susan Sumner and Blake R. Rushing and Sergey A. Krupenko},
  journal = {Cells},
  year = {2026},
  month = nov,
  doi = {10.3390/cells15212026},
  url = {https://www.mdpi.com/2073-4409/15/21/2026},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Genetic Variations in the Folate Regulatory Enzyme ALDH1L1: Impact on Cell Metabolism, Proliferation, and Motility
AU  - Halle M. Meyers
AU  - Amira A. Abdellatef
AU  - Natalia I. Krupenko
AU  - Baba Mass
AU  - Venkata Saroja Voruganti
AU  - Susan Sumner
AU  - Blake R. Rushing
AU  - Sergey A. Krupenko
PY  - 2026
DA  - 2026/11/06
JO  - Cells
DO  - 10.3390/cells15212026
UR  - https://www.mdpi.com/2073-4409/15/21/2026
AB  - In humans, six common non-synonymous exonic single-nucleotide polymorphisms in ALDH1L1 lead to ten enzyme haplotypes. Since ALDH1L1 is a metabolic regulator and a candidate tumor suppressor, we studied how haplotype variants affect metabotypes, proliferation and motility. Using lentiviral delivery to A549 and PC3 cells, we have generated two cell panels, with each cell line in the panel carrying one of ten ALDH1L1 haplotype variants. Untargeted metabolomics revealed strong differences in metabotypes between cells carrying ALDH1L1 variants. Certain ALDH1L1 variants had decreased ability to regulate one-carbon metabolism and downstream pathways, including amino acid and glutathione metabolism, nucleotide biosynthesis, and the TCA cycle. The direct comparison of A549 and PC3 cells using an untargeted metabolomic dataset also showed that the two cell lines have vastly different metabotypes. In agreement with this finding, the analysis of A549 and PC3 ALDH1L1 haplotype panels suggested that the ALDH1L1-linked metabolic regulation is strongly influenced by specific cellular metabotypes and genetic background. ALDH1L1 variants also exhibited reduced inhibition of cellular proliferation and motility compared to the most common haplotype, which supports further investigation of their potential relevance to individual risk of metabolic disorders.
SN  - 2073-4409
ER  -