To investigate the effects of varying NAT1 activity in different cell-lines, mitochondrial oxidative phosphorylation, aerobic glycolysis and mitochondrial fuel usage was quantified in a panel of human cell-lines. As NAT1 activity increased, mitochondrial reserve respiratory capacity increased while aerobic glycolysis decreased. In addition, phosphorylation of PDH-E1α in these cells limited their ability to use glucose as a primary fuel source. Those cells with high NAT1 activity exhibited a quiescent metabolic phenotype and proliferated more slowly. This might explain, in part, why some cancer patients with low NAT1 expression in their tumour tissue show poorer survival outcomes compared to those with high NAT1 expression. The current study demonstrated that NAT1 enzymatic activity is important for metabolism in cancer cell-lines and increasing NAT1 activity may better equip cells to survive under stressed conditions by increasing reserve respiratory capacity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbamcr.2025.119929 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Arylamine N-acetyltransferase 1 expression predicts glucose dependence and mitochondrial bioenergetics in cancer cells.
Biochim Biophys Acta Mol Cell Res
March 2025
Laboratory for Molecular and Cellular Pharmacology, School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia. Electronic address:
To investigate the effects of varying NAT1 activity in different cell-lines, mitochondrial oxidative phosphorylation, aerobic glycolysis and mitochondrial fuel usage was quantified in a panel of human cell-lines. As NAT1 activity increased, mitochondrial reserve respiratory capacity increased while aerobic glycolysis decreased. In addition, phosphorylation of PDH-E1α in these cells limited their ability to use glucose as a primary fuel source.
View Article and Find Full Text PDFA critical genetic interaction between Gemin3/Ddx20 and translation initiation factor NAT1/eIF4G2 drives development.
Dev Biol
February 2025
Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, Malta; Centre for Molecular Medicine and Biobanking, Biomedical Sciences Building, University of Malta, Msida, Malta. Electronic address:
Gemin3 (Gem3) or DEAD-box RNA helicase 20 (Ddx20) has been mostly implicated in the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs) as part of the SMN-Gemins complex. Nonetheless, several studies have hinted at its participation in diverse snRNP-independent activities. Here, we utilised a narrow unbiased genetic screen to discover novel Gem3 interactors in Drosophila with the aim of gaining better insights on its function in vivo.
View Article and Find Full Text PDFCharacterization of NAT, GST, and CYP2E1 Genetic Variation in Sub-Saharan African Populations: Implications for Treatment of Tuberculosis and Other Diseases.
Clin Pharmacol Ther
January 2025
Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Tuberculosis (TB) is a major health burden in Africa. Although TB is treatable, anti-TB drugs are associated with adverse drug reactions (ADRs), which are partly attributed to pharmacogenetic variation. The distribution of star alleles (haplotypes) influencing anti-TB drug metabolism is unknown in many African populations.
View Article and Find Full Text PDFEnhancement of detoxification of xenobiotic aromatic amine dyes by N-acetyltransferase 1 (NAT1) enzyme on human keratinocytes cells through structural modification.
Environ Toxicol Pharmacol
March 2025
Department of Pharmacy and Pharmaceutical Sciences, National University of Singapore, Lower Kent Ridge Road, 4 Science Drive 2, 117544, Singapore. Electronic address:
The metabolic conversion of aromatic amines to N-acetylated forms in skin and keratinocytes depends on N-acetyltransferase-1 (NAT1). Common hair color ingredient such as para-phenylenediamine (PPD) causes allergic contact dermatitis. We explored how different electronic substituents on PPD aided NAT1 enzyme biotransform oxidative arylamine (AA) compounds G1-G13 by N-acetylation, NAT-1 activity assays, metabolism, and in vitro clearance investigations in human keratinocytes, while identifying NAT-1 protein levels by Western blot and qRT-PCR.
View Article and Find Full Text PDFSpermidine mediates acetylhypusination of RIPK1 to suppress diabetes onset and progression.
Nat Cell Biol
December 2024
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
It has been established that N-acetyltransferase (murine NAT1 (mNAT1) and human NAT2 (hNAT2)) mediates insulin sensitivity in type 2 diabetes. Here we show that mNAT1 deficiency leads to a decrease in cellular spermidine-a natural polyamine exhibiting health-protective and anti-ageing effects-but understanding of its mechanism is limited. We identify that mNAT1 and hNAT2 modulate a type of post-translational modification involving acetylated spermidine, which we name acetylhypusination, on receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-a key regulator of inflammation and cell death.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!