Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Bluemel, G; Planque, M; Madreiter-Sokolowski, CT; Haitzmann, T; Hrzenjak, A; Graier, WF; Fendt, SM; Olschewski, H; Leithner, K.
PCK2 opposes mitochondrial respiration and maintains the redox balance in starved lung cancer cells.
Free Radic Biol Med. 2021; 176:34-45
Doi: 10.1016/j.freeradbiomed.2021.09.007
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Leithner Katharina
- Co-Autor*innen der Med Uni Graz
- Blümel Gabriele Agnes
- Graier Wolfgang
- Haitzmann Theresa
- Hrzenjak Andelko
- Madreiter-Sokolowski Corina
- Olschewski Horst
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- Abstract:
- Cancer cells frequently lack nutrients like glucose, due to insufficient vascular networks. Mitochondrial phosphoenolpyruvate carboxykinase, PCK2, has recently been found to mediate partial gluconeogenesis and hence anabolic metabolism in glucose starved cancer cells. Here we show that PCK2 acts as a regulator of mitochondrial respiration and maintains the redox balance in nutrient-deprived human lung cancer cells. PCK2 silencing increased the abundance and interconversion of tricarboxylic acid (TCA) cycle intermediates, augmented mitochondrial respiration and enhanced glutathione oxidation under glucose and serum starvation, in a PCK2 re-expression reversible manner. Moreover, enhancing the TCA cycle by PCK2 inhibition severely reduced colony formation of lung cancer cells under starvation. As a conclusion, PCK2 contributes to maintaining a reduced glutathione pool in starved cancer cells besides mediating the biosynthesis of gluconeogenic/glycolytic intermediates. The study sheds light on adaptive responses in cancer cells to nutrient deprivation and shows that PCK2 confers protection against respiration-induced oxidative stress.
- Find related publications in this database (Keywords)
- Cancer metabolism
- Gluconeogenesis
- Adaptation
- Metabolic flexibility
- Mitochondria
- Respiration
- Redox balance