Metabolomics

Dataset Information

0

Hif1α-Dependent Uncoupling Of Glycolysis Suppresses Tumor Cell Proliferation


ABSTRACT: Hypoxia-inducible factor-1α (HIF1α) attenuates mitochondrial activity while promoting glycolysis. Paradoxically, it remains unknown why lower glycolysis is compromised in human clear cell renal cell carcinomas (ccRCC), in which HIF1α acts a tumor suppressor by inhibiting cell autonomous proliferation. Here we found that unexpectedly, HIF1α suppresses lower glycolysis after the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) step, leading to reduced lactate secretion in different tumor cell types when cells encounter a limited pyruvate supply such as that typically found in the tumor microenvironment in vivo. This is because HIF1α-dependent attenuation of mitochondrial oxygen consumption increases the NADH/NAD+ ratio that suppresses the activity of NADH-sensitive GAPDH glycolytic enzyme. This is manifested when pyruvate supply is limited since pyruvate acts as an electron acceptor that prevents the increment of the NADH/NAD+ ratio. Furthermore, this anti-glycolytic function provides a molecular basis to explain how HIF1α can suppress tumor cell proliferation by increasing the NADH/NAD+ ratio.

INSTRUMENT(S): Gas Chromatography MS - positive, Liquid Chromatography MS - negative - hilic

SUBMITTER: Juan Fernandez-Garcia 

PROVIDER: MTBLS8901 | MetaboLights | 2024-03-15

REPOSITORIES: MetaboLights

Dataset's files

Source:
Action DRS
MTBLS8901 Other
FILES Other
a_MTBLS8901_GC-MS_positive__metabolite_profiling.txt Txt
a_MTBLS8901_LC-MS_negative_hilic_metabolite_profiling.txt Txt
i_Investigation.txt Txt
Items per page:
1 - 5 of 8
altmetric image

Publications


Hypoxia-inducible factor-1α (HIF1α) attenuates mitochondrial activity while promoting glycolysis. However, lower glycolysis is compromised in human clear cell renal cell carcinomas, in which HIF1α acts as a tumor suppressor by inhibiting cell-autonomous proliferation. Here, we find that, unexpectedly, HIF1α suppresses lower glycolysis after the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) step, leading to reduced lactate secretion in different tumor cell types when cells encounter a limited  ...[more]

Similar Datasets

2020-10-02 | GSE143977 | GEO
2019-12-05 | GSE135831 | GEO
2023-06-01 | GSE210562 | GEO
2023-09-01 | GSE220876 | GEO
2022-02-25 | PXD022547 | Pride
2024-08-01 | GSE244814 | GEO
2021-10-27 | GSE178748 | GEO
2017-05-15 | GSE95341 | GEO
2021-07-29 | GSE180640 | GEO
2024-07-02 | GSE243640 | GEO