Institute of Cardiology, Lithuanian University of Health Sciences, LT 44307 Kaunas, Lithuania.
Institute of Pharmaceutical Technologies, Lithuanian University of Health Sciences, LT 44307 Kaunas, Lithuania.
Int J Mol Sci. 2019 Mar 18;20(6):1348. doi: 10.3390/ijms20061348.
Both cytosolic fatty acid synthesis (FAS) and mitochondrial fatty acid oxidation (FAO) have been shown to play a role in the survival and proliferation of cancer cells. This study aimed to confirm experimentally whether FAS and FAO coexist in breast cancer cells (BCC). By feeding cells with C-labeled glutamine and measuring labeling patterns of TCA intermediates, it was possible to show that part of the cytosolic acetyl-CoA used in lipid synthesis is also fed back into the mitochondrion via fatty acid degradation. This results in the transfer of reductive potential from the cytosol (in the form of NADPH) to the mitochondrion (in the form of NADH and FADH₂). The hypothesized mechanism was further confirmed by blocking FAS and FAO with siRNAs. Exposure to staurosporine (which induces ROS production) resulted in the disruption of simultaneous FAS and FAO, which could be explained by NADPH depletion.
胞质脂肪酸合成（FAS）和线粒体脂肪酸氧化（FAO）都被证明在癌细胞的存活和增殖中发挥作用。本研究旨在通过实验证实乳腺癌细胞（BCC）中是否同时存在 FAS 和 FAO。通过用 C 标记的谷氨酰胺喂养细胞并测量 TCA 中间产物的标记模式，可以表明用于脂质合成的部分胞质乙酰辅酶 A 也通过脂肪酸降解反馈到线粒体中。这导致还原性潜力从细胞质（以 NADPH 的形式）转移到线粒体（以 NADH 和 FADH₂的形式）。该假设的机制进一步通过 siRNA 阻断 FAS 和 FAO 得到证实。暴露于 staurosporine（诱导 ROS 产生）导致同时的 FAS 和 FAO 中断，这可以通过 NADPH 耗竭来解释。
