Mitochondria regulate intestinal stem cell proliferation and epithelial homeostasis through FOXO.
Mitochondria regulate intestinal stem cell proliferation and epithelial homeostasis through FOXO.
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线粒体通过 FOXO 调节肠道干细胞增殖和上皮稳态。
DOI：
10.1091/mbc.e19-10-0560
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发表时间：
2020
影响因子：
3.3
通讯作者：
Xu,Hong
中科院分区：
文献类型：
--
作者：
Zhang,Fan;Pirooznia,Mehdi;Xu,Hong
从糖酵解到氧化磷酸化的代谢转变通常与许多类型的干细胞的分化有关。然而，线粒体呼吸和干细胞行为之间的联系尚未完全了解。我们在果蝇的肠道干细胞（ISCs）中基因干扰电子传递链（ETC）复合物。我们发现携带受损ETC的ISCs增殖比正常的慢得多，产生的肠母细胞很少，不能进一步分化为肠上皮细胞。ISC增殖和谱系特化的主要障碍之一似乎是在ETC缺陷的ISC中异常升高的叉头框O（FOXO）信号传导，因为遗传抑制信号传导途径部分地恢复了肠细胞的数量。与通常的看法相反，活性氧（ROS）的积累似乎并不介导ETC突变表型。我们的研究结果表明，线粒体呼吸是必不可少的果蝇ISC增殖和谱系特化在体内，并至少部分地通过抑制内源性FOXO信号。
A metabolic transition from glycolysis to oxidative phosphorylation is often associated with differentiation of many types of stem cells. However, the link between mitochondrial respiration and stem cells’ behavior is not fully understood. We genetically disrupted electron transport chain (ETC) complexes in the intestinal stem cells (ISCs) ofDrosophila. We found that ISCs carrying impaired ETC proliferated much more slowly than normal and produced very few enteroblasts, which failed to further differentiate into enterocytes. One of the main impediments to ISC proliferation and lineage specification appeared to be abnormally elevated forkhead box O (FOXO) signaling in the ETC-deficient ISCs, as genetically suppressing the signaling pathway partially restored the number of enterocytes. Contrary to common belief, reactive oxygen species (ROS) accumulation did not appear to mediate the ETC mutant phenotype. Our results demonstrate that mitochondrial respiration is essential forDrosophilaISC proliferation and lineage specification in vivo and acts at least partially by repressing endogenous FOXO signaling.