Domenis 2011 J Bioenerg Biomembr
| Domenis R, Comelli M, Bisetto E, Mavelli I (2011) Mitochondrial bioenergetic profile and responses to metabolic inhibition in human hepatocarcinoma cell lines with distinct differentiation characteristics. J Bioenerg Biomembr 43: 493-505. |
Domenis R, Comelli M, Bisetto E, Mavelli I (2011) J Bioenerg Biomembr
Abstract: The classical view of tumour cell bioenergetics has been recently revised. Then, the definition of the mitochondrial profile is considered of fundamental importance for the development of anti-cancer therapies, but it still needs to be clarified. We investigated two human hepatocellular carcinoma cell lines: the partially differentiated HepG2 and the undifferentiated JHH-6. High-resolution respirometry revealed a marked impairment/uncoupling of OXPHOS in JHH-6 compared with HepG2, with the phosphorylation system limiting the capacity for electron transport much more in JHH-6. Blocking glycolysis or mitochondrial ATP synthase we demonstrated that in JHH-6 ATP synthase functions in reverse and consumes glycolytic ATP, thereby sustaining ฮฮจm. A higher expression level of ATP synthase Inhibitor Factor 1 (IF1), a higher extent of IF1 bound to ATP synthase and a lower ATPase/synthase capacity were documented in JHH-6. Thus, here IF1 appears to down-regulate the reverse mode of ATPsynthase activity, thereby playing a crucial role in controlling energy waste and ฮฮจm. These results, while confirming the over-expression of IF1 in cancer cells, are the first to indicate an inverse link between cell differentiation status and IF1 (expression level and regulatory function).
โข O2k-Network Lab: IT_Udine_Grassi B, IT Udine Mavelli I
Labels:
Pathology: Cancer
Organism: Human Tissue;cell: Liver Preparation: Intact cells
Coupling state: OXPHOS
HRR: Oxygraph-2k
