Skolik 2017 Abstract IOC122

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What can we learn from different sugars as substrates for cancer cells?

Link: Mitochondr Physiol Network 22.01

Skolik RA, Menze MA (2017)

Event: IOC122

Otto Warburg described 61 years ago how energy production in highly proliferating cancer cells shifts from oxidative phosphorylation (OXPHOS) to glycolysis even in presence of oxygen concentrations high enough to support mitochondrial OXPHOS. When glucose is replaced by the monosaccharaide galactose, alternative energy substrates such a glutamine are utilized. This simple change dramatically shifts energy metabolism towards the mitochondrion by engaging higher rates of OXPHOS. These increased rates of OXPHOS are dependent upon cofactors such as the iron-sulfur clusters found in several of the respiratory complexes. Recent findings have revealed that the family of mitochondrial-associated NEET (CISD1 and CISD2) proteins contains labile 2Fe-2S clusters capable of transfer to apo-acceptor enzymes. Galactose treatments are currently used both as models for aging and to increase sensitivity of cancer cells to mitochondrial toxins for drug development (4). Surprisingly, a comprehensive understanding of the impact of galactose on cancer cells remains unknown. Furthermore, the impact of galactose on NEET protein expression and function has not been explored.

We hypothesize that the observed increase in OXPHOS after replacing glucose with galactose as a carbon source relies on shifts in the expression patterns of mitochondrial dehydrogenases and redox active proteins.

Here we show that HepG2 cells cultured in presence of dialyzed FBS (dFBS) and galactose show dramatic shifts in metabolism, gene expression, and mitochondrial activity. The response to galactose exposure was time dependent, with longer exposure to galactose resulting in more pronounced increases in OXPHOS capacity. Additionally, we reveal that utilization of dFBS can have broad implications on cellular physiology by changing expression of CISD1, thought to be involved in a variety of processes ranging from protection from oxidative stress to the regulation of cellular bioenergetics.


Bioblast editor: Kandolf G O2k-Network Lab: US KY Louisville Menze MA


Labels: MiParea: Respiration, Exercise physiology;nutrition;life style  Pathology: Cancer 

Organism: Human  Tissue;cell: Liver 



HRR: Oxygraph-2k 


Affiliations

Dept Biol, Univ Louisville, KY, USA. - robert.skolik@louisville.edu