Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/107868
Title: INSIGHT INTO THE BIOENERGETICS OF CLEAR CELL RENAL CELL CARCINOMA (CCRCC)
Authors: LIM HWEE YING
Keywords: clear cell Renal Cell Carcinoma (ccRCC), bioenergetics, Warburg, oxidative phosphorylation (OXPHOS), mitochondrial membrane potential (MMP), UCP
Issue Date: 19-Aug-2014
Citation: LIM HWEE YING (2014-08-19). INSIGHT INTO THE BIOENERGETICS OF CLEAR CELL RENAL CELL CARCINOMA (CCRCC). ScholarBank@NUS Repository.
Abstract: Clear cell renal cell carcinoma (ccRCC) is characterized by an increased expression of the hypoxia inducible factors (HIF) due to VHL gene mutations. Targets of HIF, namely hexokinase II, lactate dehydrogenase 5 and pyruvate dehydrogenase (PDH) kinase 1 (PDHK1) are higher than patient-matched normal tissues. PDHK1 phosphorylates and inhibits PDH whose enzymatic activity was negligible, depriving the TCA cycle of acetylCoA. Lower expression of transcription factors (mtTFA, PGC-1a and NRF1) involved in mitobiogenesis lead to the attenuated expressions and activities of the respiratory complexes, oxidative phosphorylation (OXPHOS) was therefore predicted to be compromised. However, we found that the biosynthesis of ATP, induction of mitochondrial membrane potential (MMP) and oxygen flux were measurable from the oxidation of conventional respiratory substrates in mitochondria isolated from ccRCC tumor tissues, demonstrating their ¿potential¿ for OXPHOS. Interestingly, a consistently higher basal MMP was observed in tumor, in which uncoupling proteins or metabolites could play a role.
URI: http://scholarbank.nus.edu.sg/handle/10635/107868
Appears in Collections:Master's Theses (Open)

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