Lactate metabolism is associated with mammalian mitochondria.
Lactate metabolism is associated with mammalian mitochondria.
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DOI：
10.1038/nchembio.2172
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发表时间：
2016-11
影响因子：
14.8
通讯作者：
Patti GJ
中科院分区：
文献类型：
--
作者：
Chen YJ;Mahieu NG;Huang X;Singh M;Crawford PA;Johnson SL;Gross RW;Schaefer J;Patti GJ
众所周知，发酵细胞分泌的乳酸可以被其他细胞和组织氧化或用作糖异生底物。然而，在发酵细胞本身，通常认为乳酸是为了补充NAD+而产生的，然后被分泌。在这里，我们探索了胞浆乳酸由发酵的哺乳动物细胞的线粒体代谢的可能性。我们发现，发酵的HeLa和H460细胞利用外源乳酸碳来合成很大比例的脂。利用高分辨质谱仪，我们发现富含乳酸的13C和2-2H标记物都进入了线粒体。乳酸脱氢酶(LDH)抑制剂草酸降低了在乳酸中孵育的线粒体的呼吸，但不降低在丙酮酸中孵育的线粒体的呼吸。此外，透射电子显微镜显示LDHB定位于线粒体。综上所述，我们的结果表明乳酸代谢和正在发酵的哺乳动物细胞的线粒体之间存在联系。
It is well established that lactate secreted by fermenting cells can be oxidized or used as a gluconeogenic substrate by other cells and tissues. Within the fermenting cell itself, however, it is generally assumed that lactate is produced to replenish NAD+ and then is secreted. Here we explored the possibility that cytosolic lactate is metabolized by the mitochondria of fermenting mammalian cells. We found that fermenting HeLa and H460 cells utilize exogenous lactate carbon to synthesize a large percentage of their lipids. With high-resolution mass spectrometry, we found that both 13C and 2-2H labels from enriched lactate enter the mitochondria. The lactate dehydrogenase (LDH) inhibitor oxamate decreased respiration of isolated mitochondria incubated in lactate, but not isolated mitochondria incubated in pyruvate. Additionally, transmission electron microscopy (TEM) showed that LDHB localizes to the mitochondria. Taken together, our results demonstrate a link between lactate metabolism and the mitochondria of fermenting mammalian cells.