The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Quiescent Fibroblasts Exhibit High Metabolic Activity
Open accessAbstract
Many cells in mammals exist in the state of quiescence, which is characterized by reversible exit from the cell cycle. Quiescent cells are widely reported to exhibit reduced size, nucleotide synthesis, and metabolic activity. Much lower glycolytic rates have been reported in quiescent compared with proliferating lymphocytes. In contrast, we show here that primary human fibroblasts continue to exhibit high metabolic rates when induced into quiescence via contact inhibition. By monitoring isotope labeling through metabolic pathways and quantitatively identifying fluxes from the data, we show that contact-inhibited fibroblasts utilize glucose in all branches of central carbon metabolism at rates similar to those of proliferating cells, with greater overflow flux from the pentose phosphate pathway back to glycolysis. Inhibition of the pentose phosphate pathway resulted in apoptosis preferentially in quiescent fibroblasts. By feeding the cells labeled glutamine, we also detected a "backwards" flux in the tricarboxylic acid cycle from α-ketoglutarate to citrate that was enhanced in contact-inhibited fibroblasts; this flux likely contributes to shuttling of NADPH from the mitochondrion to cytosol for redox defense or fatty acid synthesis. The high metabolic activity of the fibroblasts was directed in part toward breakdown and resynthesis of protein and lipid, and in part toward excretion of extracellular matrix proteins. Thus, reduced metabolic activity is not a hallmark of the quiescent state. Quiescent fibroblasts, relieved of the biosynthetic requirements associated with generating progeny, direct their metabolic activity to preservation of self integrity and alternative functions beneficial to the organism as a whole.
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The CD28 Signaling Pathway Regulates Glucose Metabolism
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Perspective Article: Tissue repair, contraction, and the myofibroblast
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Self-citationKinetic flux profiling of nitrogen assimilation in Escherichia coli
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Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia
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Reductive carboxylation supports growth in tumour cells with defective mitochondria
Mullen, A. R., Wheaton, W. W., Jin, E. S., Chen, P.-H., Sullivan, L. B., Cheng, T., Yang, Y., Linehan, W. M., Chandel, N. S., & DeBerardinis, R. J. (2012) · Nature · doi:10.1038/nature10642 · Cited by 1,328
Quantitative flux analysis reveals folate-dependent NADPH production
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Self-citationLactate: the ugly duckling of energy metabolism
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Metadata
- Authors
- Lemons, J. M. S., Feng, X.-J., Bennett, B. D., Legesse-Miller, A., Johnson, E. L., Raitman, I., Pollina, E. A., Rabitz, H. A., Rabinowitz, J. D., & Coller, H. A.
- Venue
- PLoS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-10-19
- Volume
- 8
- Issue
- 10
- Pages
- e1000514
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- OpenAlex
- W1999434929
- Cited by
- 382
- References
- 9
- FWCI
- 6.41
- Type
- journal article
- Language
- en
- Open access
- gold
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- Lemons, J. M. S., Feng, X.-J., Bennett, B. D., Legesse-Miller, A., Johnson, E. L., Raitman, I., Pollina, E. A., Rabitz, H. A., Rabinowitz, J. D., & Coller, H. A. (2010). Quiescent Fibroblasts Exhibit High Metabolic Activity. PLoS Biology. https://doi.org/10.1371/journal.pbio.1000514
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