Abstract
Uncoupling protein 2 (UCP2) is often upregulated in cancer cells. The UCP2 upregulation is positively correlated with enhanced proliferation, tumorigenesis, and metabolic alterations, thus suggesting that UCP2 upregulation can play a key role in sensing metabolic changes to promote tumorigenesis. To determine the global metabolic impact of UCP2 upregulation, 13C6 glucose as a source molecule is used to “trace” the metabolic fate of carbon atoms derived from glucose. UCP2 overexpression in skin epidermal cells enhances the incorporation of 13C label to pyruvate, tricarboxylic acid cycle intermediates, nucleotides, and amino acids, suggesting that UCP2 upregulation reprograms cellular metabolism toward macromolecule synthesis. To the best of our knowledge, this is the first study to bring to light the overall metabolic differences caused by UCP2 upregulation.
| Original language | English |
|---|---|
| Article number | 1800353 |
| Journal | Proteomics |
| Volume | 19 |
| Issue number | 4 |
| DOIs | |
| State | Published - Feb 2019 |
Bibliographical note
Publisher Copyright:© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Funding
A.N.L. and Y.Z. designed the experiments. A.S., T.C., and P.S. performed the experiments. A.S., T.C., P.S., H.W.N., A.N.L., and Y.Z. analyzed the data. A.S., A.N.L., and Y.Z. wrote the manuscript. This work was supported in part by a pilot grant from 1U24DK097215-01A1 (RCSIRM UKy) awarded to Y.Z. NMR spectra and IC-MS were recorded at the Center for Environmental Systems Biochemistry, University of Kentucky, supported in part by NCI, National Institutes of Health, Cancer Center Support Grant P30 CA177558.
| Funders | Funder number |
|---|---|
| National Institutes of Health (NIH) | |
| National Childhood Cancer Registry – National Cancer Institute | P30CA177558 |
| University of Kentucky |
Keywords
- bioenergetics
- metabolite profiling
- metabolomics
- mitochondrial metabolism
- tumorigenesis
- uncoupling protein 2
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
