Loss of human arylamine N-acetyltransferase I regulates mitochondrial function by inhibition of the pyruvate dehydrogenase complex
2019
Wang, Lili | Minchin, Rodney F. | Essebier, Patricia J. | Butcher, Neville J.
Human arylamine N-acetyltransferase 1 (NAT1) has been widely reported to affect cancer cell growth and survival and recent studies suggest it may alter cell metabolism. In this study, the effects of NAT1 deletion on mitochondrial function was examined in 2 human cell lines, breast carcinoma MDA-MB-231 and colon carcinoma HT-29 cells. Using a Seahorse XFe96 Flux Analyzer, NAT1 deletion was shown to decrease oxidative phosphorylation with a significant loss in respiratory reserve capacity in both cell lines. There also was a decrease in glycolysis without a change in glucose uptake. The changes in mitochondrial function was due to a decrease in pyruvate dehydrogenase activity, which could be reversed with the pyruvate dehydrogenase kinase inhibitor dichloroacetate. In the MDA-MB-231 and HT-29 cells, pyruvate dehydrogenase activity was attenuated either by an increase in phosphorylation or a decrease in total protein expression. These results may help explain some of the cellular events that have been reported recently in cell and animal models of NAT1 deficiency.
اظهر المزيد [+] اقل [-]الكلمات المفتاحية الخاصة بالمكنز الزراعي (أجروفوك)
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