| 1. |
- Lau, Allison N., et al.
(författare)
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Dissecting cell-type-specific metabolism in pancreatic ductal adenocarcinoma
- 2020
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Ingår i: eLife. - 2050-084X. ; 9, s. 1-35
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Tidskriftsartikel (refereegranskat)abstract
- Tumors are composed of many different cell types including cancer cells, fibroblasts, and immune cells. Dissecting functional metabolic differences between cell types within a mixed population can be challenging due to the rapid turnover of metabolites relative to the time needed to isolate cells. To overcome this challenge, we traced isotope-labeled nutrients into macromolecules that turn over more slowly than metabolites. This approach was used to assess differences between cancer cell and fibroblast metabolism in murine pancreatic cancer organoid-fibroblast co-cultures and tumors. Pancreatic cancer cells exhibited increased pyruvate carboxylation relative to fibroblasts, and this flux depended on both pyruvate carboxylase and malic enzyme 1 activity. Consequently, expression of both enzymes in cancer cells was necessary for organoid and tumor growth, demonstrating that dissecting the metabolism of specific cell populations within heterogeneous systems can identify dependencies that may not be evident from studying isolated cells in culture or bulk tissue.
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| 2. |
- Luengo, Alba, et al.
(författare)
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Increased demand for NAD + relative to ATP drives aerobic glycolysis
- 2021
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Ingår i: Molecular Cell. - : Elsevier BV. - 1097-4164 .- 1097-2765. ; 81:4, s. 691-707.e6
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Tidskriftsartikel (refereegranskat)abstract
- Aerobic glycolysis, or preferential fermentation of glucose-derived pyruvate to lactate despite available oxygen, is associated with proliferation across many organisms and conditions. To better understand that association, we examined the metabolic consequence of activating the pyruvate dehydrogenase complex (PDH) to increase pyruvate oxidation at the expense of fermentation. We find that increasing PDH activity impairs cell proliferation by reducing the NAD+/NADH ratio. This change in NAD+/NADH is caused by increased mitochondrial membrane potential that impairs mitochondrial electron transport and NAD+ regeneration. Uncoupling respiration from ATP synthesis or increasing ATP hydrolysis restores NAD+/NADH homeostasis and proliferation even when glucose oxidation is increased. These data suggest that when demand for NAD+ to support oxidation reactions exceeds the rate of ATP turnover in cells, NAD+ regeneration by mitochondrial respiration becomes constrained, promoting fermentation, despite available oxygen. This argues that cells engage in aerobic glycolysis when the demand for NAD+ is in excess of the demand for ATP. Aerobic glycolysis is associated with proliferation in many biological contexts, yet what drives this phenotype has not been fully explained. Luengo et al. show that cells engage in aerobic glycolysis when the demand for NAD+ exceeds the demand for ATP, which leads to impaired NAD+ regeneration by mitochondrial respiration.
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| 3. |
- Zhang, Qiong, et al.
(författare)
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A series of Zn(II) terpyridine complexes with enhanced two-photon-excited fluorescence for in vitro and in vivo bioimaging
- 2015
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Ingår i: Journal of materials chemistry. B. - : ROYAL SOC CHEMISTRY. - 2050-750X .- 2050-7518. ; 3:36, s. 7213-7221
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Tidskriftsartikel (refereegranskat)abstract
- It is still a challenge to obtain two-photon excited fluorescent bioimaging probes with intense emission, high photo-stability and low cytotoxicity. In the present work, four Zn(II)-coordinated complexes (1-4) constructed from two novel D-A and D-p-A ligands (L-1 and L-2) are investigated both experimentally and theoretically, aiming to explore efficient two-photon probes for bioimaging. Molecular geometry optimization used for theoretical calculations is achieved using the crystallographic data. Notably, the results indicate that complexes 1 and 2 display enhanced two-photon absorption (2PA) cross sections compared to their corresponding D-A ligand (L1). Furthermore, it was found that complex 1 has the advantages of moderate 2PA cross section in the near-infrared region, longer fluorescence lifetime, higher quantum yield, good biocompatibility and enhanced two-photon excited fluorescence. Therefore, complex 1 is evaluated as a bioimaging probe for in vitro imaging of HepG2 cells, in which it is observed under a two-photon scanning microscope that complex 1 exhibits effective co-staining with endoplasmic reticulum (ER) and nuclear membrane; as well as for in vivo imaging of zebrafish larva, in which it is observed that complex 1 exhibits specificity in the intestinal system.
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