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Selected Publication:

Type of publication: Journal Article
Type of document: Full Paper

Year: 2019

Authors: Rupprecht, A; Moldzio, R; Mödl, B; Pohl, EE

Title: Glutamine regulates mitochondrial uncoupling protein 2 to promote glutaminolysis in neuroblastoma cells.

Source: Biochim Biophys Acta Bioenerg. 2019; 1860(5):391-401



Authors Vetmeduni Vienna:

Moldzio Rudolf
Pohl Elena
Rupprecht Anne

Vetmed Research Units
Institute for Medical Biochemistry
Institute of Physiology, Pathohysiology and Biophysics, Unit of Physiology and Biophysics


Abstract:
Mitochondrial uncoupling protein 2 (UCP2) is highly abundant in rapidly proliferating cells that utilize aerobic glycolysis, such as stem cells, cancer cells, and cells of the immune system. However, the function of UCP2 has been a longstanding conundrum. Considering the strict regulation and unusually short life time of the protein, we propose that UCP2 acts as a "signaling protein" under nutrient shortage in cancer cells. We reveal that glutamine shortage induces the rapid and reversible downregulation of UCP2, decrease of the metabolic activity and proliferation of neuroblastoma cells, that are regulated by glutamine per se but not by glutamine metabolism. Our findings indicate a very rapid (within 1 h) metabolic adaptation that allows the cell to survive by either shifting its metabolism to the use of the alternative fuel glutamine or going into a reversible, more quiescent state. The results imply that UCP2 facilitates glutamine utilization as an energetic fuel source, thereby providing metabolic flexibility during glucose shortage. The targeting UCP2 by drugs to intervene with cancer cell metabolism may represent a new strategy for treatment of cancers resistant to other therapies.Copyright © 2019. Published by Elsevier B.V.

Keywords Pubmed: Animals
Cell Line, Tumor
Cell Proliferationgenetics
Down-Regulation
Energy Metabolismgenetics
Gene Expression Regulation, Neoplastic
Glucosegeneticsmetabolism
Glutaminegeneticsmetabolism
Mice
Neoplasm Proteinsbiosynthesisgenetics
Neuroblastomageneticsmetabolismpathology
Uncoupling Protein 2biosynthesisgenetics

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