Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells.

中文翻译：

---

通过线粒体丙酮酸代谢控制肠道干细胞的功能和增殖。

大多数分化的细胞通过糖酵解将葡萄糖在胞质溶胶中转化为丙酮酸，然后在线粒体中将丙酮酸氧化。这些过程由线粒体丙酮酸载体（MPC）连接，而线粒体丙酮酸载体是有效摄取线粒体丙酮酸所必需的。相比之下，包括许多癌细胞和干细胞在内的增生性细胞可强有力地进行糖酵解，但会限制线粒体丙酮酸的部分氧化。我们试图了解从糖酵解到丙酮酸氧化的这种转变在干细胞维持和分化中的作用。Lgr5-EGFP阳性干细胞中MPC的丢失，或用MPC抑制剂治疗肠道类器官，会增加增殖并扩大干细胞区室。同样，果蝇肠道干细胞中MPC的基因缺失也可增加增殖，而MPC的过表达抑制干细胞的增殖。这些数据表明限制线粒体丙酮酸的代谢对于维持肠道干细胞的增殖是必要和充分的。