Unlabelled: Mitochondrial dysfunction plays a significant role in the metabolic flexibility of cancer cells. This study aimed to investigate the metabolic alterations due to Coenzyme Q depletion in MCF-7 cells.
Method: The Coenzyme Q depletion was induced by competitively inhibiting with 4-nitrobenzoate the coq2 enzyme, which catalyzes one of the final reactions in the biosynthetic pathway of CoQ. The bioenergetic and metabolic characteristics of control and coenzyme Q depleted cells were investigated using polarographic and spectroscopic assays. The effect of CoQ depletion on cell growth was analyzed in different metabolic conditions.
Results: we showed that cancer cells could cope from energetic and oxidative stress due to mitochondrial dysfunction by reshaping their metabolism. In CoQ depleted cells, the glycolysis was upregulated together with increased glucose consumption, overexpression of GLUT1 and GLUT3, as well as activation of pyruvate kinase (PK). Moreover, the lactate secretion rate was reduced, suggesting that the pyruvate flux was redirected, toward anabolic pathways. Finally, we found a different expression pattern in enzymes involved in glutamine metabolism, and TCA cycle in CoQ depleted cells in comparison to controls.
Conclusion: This work elucidated the metabolic alterations in CoQ-depleted cells and provided an insightful understanding of cancer metabolism targeting.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795339 | PMC |
| http://dx.doi.org/10.3390/ijms22010198 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation.
Nat Commun
January 2025
The Picower Institute for Learning and Memory, MIT, Cambridge, MA, USA.
Many essential proteins require pyridoxal 5'-phosphate, the active form of vitamin B6, as a cofactor for their activity. These include enzymes important for amino acid metabolism, one-carbon metabolism, polyamine synthesis, erythropoiesis, and neurotransmitter metabolism. A third of all mammalian pyridoxal 5'-phosphate-dependent enzymes are localized in the mitochondria; however, the molecular machinery involved in the regulation of mitochondrial pyridoxal 5'-phosphate levels in mammals remains unknown.
View Article and Find Full Text PDFProgrammed neurite degeneration in human central nervous system neurons driven by changes in NAD metabolism.
Cell Death Dis
January 2025
In vitro Toxicology and Biomedicine, Dept. inaugurated by the Doerenkamp-Zbinden foundation, University of Konstanz, 78457, Konstanz, Germany.
Neurite degeneration (ND) precedes cell death in many neurodegenerative diseases. However, it remains unclear how this compartmentalized cell death process is orchestrated in the central nervous system (CNS). The establishment of a CNS axotomy model (using modified 3D LUHMES cultures) allowed us to study metabolic control of ND in human midbrain-derived neurons without the use of toxicants or other direct disturbance of cellular metabolism.
View Article and Find Full Text PDFNicotinamide adenine dinucleotide supplementation fails to enhance anesthetic recovery in rodents.
Sci Rep
January 2025
Department of Anesthesiology, Perioperative, and Pain Medicine, School of Medicine, Stanford University, Stanford, USA.
Nicotinamide Adenine Dinucleotide (NAD) is implicated in bioenergetics, DNA repair, and senescence. Depletion of NAD is associated with aging and neurodegenerative disease, prompting a growing interest in NAD supplementation. With rising over-the-counter use of NAD, understanding their impact on anesthetic recovery becomes essential.
View Article and Find Full Text PDFCYP3A5 promotes glioblastoma stemness and chemoresistance through fine-tuning NAD/NADH ratio.
J Exp Clin Cancer Res
January 2025
School of Medicine, Chinese PLA General Hospital, Nankai University, Beijing, China.
Background: Glioblastoma multiforme (GBM) exhibits a cellular hierarchy with a subpopulation of stem-like cells known as glioblastoma stem cells (GSCs) that drive tumor growth and contribute to treatment resistance. NAD(H) emerges as a crucial factor influencing GSC maintenance through its involvement in diverse biological processes, including mitochondrial fitness and DNA damage repair. However, how GSCs leverage metabolic adaptation to obtain survival advantage remains elusive.
View Article and Find Full Text PDFPrecision targeting of fat metabolism in triple negative breast cancer with a biotinylated copolymer.
J Mater Chem B
January 2025
Centre for Healthcare Science and Technology, Indian Institute of Engineering Science Technology, Shibpur, Howrah-711103, West Bengal, India.
Mitochondrial CPT1-mediated fatty acid β-oxidation (FAO) critically contributes to the accelerated metastatic expansion of triple negative breast cancer (TNBC). Hence, inhibition of FAO through active CPT1 targeting could be a promising therapeutic approach in anti-TNBC therapies. Herein, we strategically synthesized a pyrene chain end labelled copolymer bearing biotin pendants, CP4, that actively targets CPT1 and efficiently blocks FAO in metastatic TNBC.
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!