Istituto di Biomembrane e Bioenergetica, Consiglio Nazionale delle Ricerche, Bari, Italy.
FEBS Lett. 2013 Mar 1;587(5):467-73. doi: 10.1016/j.febslet.2013.01.011. Epub 2013 Jan 17.
Although D-lactate metabolism has been shown to occur in a variety of mitochondria, the metabolic fate of D-lactate in cancer cells has never been investigated, as it is believed to be exported to the extracellular phase. We show that mitochondria from both cancer (PC-3) and normal (PNT1A) prostate cells can metabolize D-lactate in an energy competent manner. This is due to the mitochondrial D-lactate dehydrogenase, a membrane flavoprotein, the activity and protein level of which are higher in PC-3 than in PNT1A cells, as detected by both kinetic and immunological analysis. D-Lactate can enter prostate mitochondria and cause the export of newly synthesized malate in a carrier-mediated manner, with the rate of malate efflux from mitochondria twofold higher in cancer.
尽管已经证明 D-乳酸在各种线粒体中都有代谢，但由于人们认为 D-乳酸会被运出细胞外，因此从未研究过癌细胞中 D-乳酸的代谢命运。我们发现，来自前列腺癌细胞（PC-3）和正常细胞（PNT1A）的线粒体都可以以能量依赖的方式代谢 D-乳酸。这是由于线粒体 D-乳酸脱氢酶是一种膜黄素蛋白，其活性和蛋白水平在 PC-3 细胞中高于 PNT1A 细胞，这一点通过动力学和免疫分析都得到了证实。D-乳酸可以进入前列腺线粒体，并以载体介导的方式导致新合成的苹果酸的输出，而癌细胞中苹果酸从线粒体的流出速率是正常细胞的两倍。
