Department of Pharmacy and Biotechnology, FABIT, University of Bologna, 6, 40126 Bologna, Italy.
Int J Mol Sci. 2020 Dec 28;22(1):198. doi: 10.3390/ijms22010198.
Mitochondrial dysfunction plays a significant role in the metabolic flexibility of cancer cells. This study aimed to investigate the metabolic alterations due to Coenzyme Q depletion in MCF-7 cells.
The Coenzyme Q depletion was induced by competitively inhibiting with 4-nitrobenzoate the coq2 enzyme, which catalyzes one of the final reactions in the biosynthetic pathway of CoQ. The bioenergetic and metabolic characteristics of control and coenzyme Q depleted cells were investigated using polarographic and spectroscopic assays. The effect of CoQ depletion on cell growth was analyzed in different metabolic conditions.
we showed that cancer cells could cope from energetic and oxidative stress due to mitochondrial dysfunction by reshaping their metabolism. In CoQ depleted cells, the glycolysis was upregulated together with increased glucose consumption, overexpression of GLUT1 and GLUT3, as well as activation of pyruvate kinase (PK). Moreover, the lactate secretion rate was reduced, suggesting that the pyruvate flux was redirected, toward anabolic pathways. Finally, we found a different expression pattern in enzymes involved in glutamine metabolism, and TCA cycle in CoQ depleted cells in comparison to controls.
This work elucidated the metabolic alterations in CoQ-depleted cells and provided an insightful understanding of cancer metabolism targeting.
线粒体功能障碍在癌细胞的代谢灵活性中起着重要作用。本研究旨在研究 CoQ 耗竭在 MCF-7 细胞中引起的代谢变化。
通过竞争性抑制 coq2 酶（催化 CoQ 生物合成途径中的最后一个反应之一）用 4-硝基苯甲酸诱导 CoQ 耗竭。使用极谱法和光谱法研究对照和辅酶 Q 耗竭细胞的生物能和代谢特征。分析 CoQ 耗竭对不同代谢条件下细胞生长的影响。
我们表明，癌细胞可以通过重塑其代谢来应对由于线粒体功能障碍引起的能量和氧化应激。在 CoQ 耗竭的细胞中，糖酵解被上调，同时葡萄糖消耗增加，GLUT1 和 GLUT3 过表达，以及丙酮酸激酶 (PK) 激活。此外，乳酸分泌率降低，表明丙酮酸通量被重新定向，进入合成代谢途径。最后，我们发现 CoQ 耗竭细胞中与对照相比，谷氨酰胺代谢和 TCA 循环中的酶表达模式不同。
这项工作阐明了 CoQ 耗竭细胞中的代谢变化，并为靶向癌症代谢提供了深入的了解。
