Altering the Mitochondrial Fatty Acid Synthesis (mtFASII) Pathway Modulates Cellular Metabolic States and Bioactive Lipid Profiles as Revealed by Metabolomic Profiling.
Altering the Mitochondrial Fatty Acid Synthesis (mtFASII) Pathway Modulates Cellular Metabolic States and Bioactive Lipid Profiles as Revealed by Metabolomic Profiling.
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DOI：
10.1371/journal.pone.0151171
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Murdock DG
中科院分区：
文献类型：
--
作者：
Clay HB;Parl AK;Mitchell SL;Singh L;Bell LN;Murdock DG
尽管存在胞质脂肪酸合成途径，但线粒体保留了其自身通过线粒体脂肪酸合成（mtFASII）途径产生脂肪酸的手段。其保存的原因尚未阐明。因此，为了更好地了解mtFASII在细胞中的作用，我们使用薄层色谱法来表征mtFASII途径对所选线粒体脂质的脂肪酸组成的贡献。接下来，我们对HeLa细胞进行了代谢组学分析，其中mtFASII途径功能低下（通过敲低线粒体酰基载体蛋白ACP）或功能亢进（通过过表达线粒体烯酰辅酶A还原酶MECR）。我们的研究结果表明，mtFASII途径有助于很少的脂肪酸组成的线粒体脂质物种检查。此外，mtFASII功能的丧失导致生化途径的变化，表明葡萄糖利用和氧化还原状态的改变。有趣的是，包括溶血磷脂和鞘脂在内的生物活性脂质的水平与mtFASII功能直接相关，表明mtFASII可能参与生物活性脂质水平的调节。mtFASII对生物活性脂质水平的调节暗示该途径是细胞内信号传导的介体。
Despite the presence of a cytosolic fatty acid synthesis pathway, mitochondria have retained their own means of creating fatty acids via the mitochondrial fatty acid synthesis (mtFASII) pathway. The reason for its conservation has not yet been elucidated. Therefore, to better understand the role of mtFASII in the cell, we used thin layer chromatography to characterize the contribution of the mtFASII pathway to the fatty acid composition of selected mitochondrial lipids. Next, we performed metabolomic analysis on HeLa cells in which the mtFASII pathway was either hypofunctional (through knockdown of mitochondrial acyl carrier protein, ACP) or hyperfunctional (through overexpression of mitochondrial enoyl-CoA reductase, MECR). Our results indicate that the mtFASII pathway contributes little to the fatty acid composition of mitochondrial lipid species examined. Additionally, loss of mtFASII function results in changes in biochemical pathways suggesting alterations in glucose utilization and redox state. Interestingly, levels of bioactive lipids, including lysophospholipids and sphingolipids, directly correlate with mtFASII function, indicating that mtFASII may be involved in the regulation of bioactive lipid levels. Regulation of bioactive lipid levels by mtFASII implicates the pathway as a mediator of intracellular signaling.