近日,研究者发现处于增殖期的非洲爪蟾的视网膜细胞采用的是有氧糖酵解而不是氧化磷酸化。表明以往Warburg effect只发生在肿瘤细胞中的认识是片面的,Warburg effect或许普遍存在于增殖代谢中。相关论文发表在近期的Nature Cell Biology上。
瓦氏效应(Warburg effect),指奥托·海因里希·瓦尔堡(Otto Heinrich Warburg)所提出的理论,认为癌细胞的生长速度远大于正常细胞的原因来自于能量的来源差别。癌细胞会偏向使用糖酵解作用取代一般正常细胞的氧化磷酸化。
Agathocleous等人发现,处于发育期的视网膜增殖的祖细胞通过糖酵解将葡萄糖转化为乳酸,即使有氧也是如此。若用糖原磷酸化酶抑制剂(glycogen phosphorylase inhibitor,GPI)处理胚胎,视网膜祖细胞仍然依赖糖酵解进行增殖。只有分化为终末分化的视网膜细胞才依赖氧化磷酸化供能。
通常认为胞外的葡萄糖对于细胞的增殖是必须的,但是此项研究表明在某些增殖细胞中糖原可作为葡萄糖产生的源泉。糖酵解对于细胞增殖的作用不是产生更多的ATP,而是生物合成,例如产生所有核苷酸合成的前体--核糖-5-磷酸。
由于整体动物水平代谢跟踪方法(whole-animal metabolic tracing methods)的广泛使用,阐明体内组织的代谢方式变得简单。而我们首先应该明白的是,在同一种组织中增殖和非增殖细胞的代谢方式可能是完全不同的。(生物谷Bioon.com)
doi:10.1038/ncb2554
PMC:
PMID:
Seeing the Warburg effect in the developing retina
Brian P. Fiske1 & Matthew G. Vander Heiden1
During development, instead of using extracellular glucose, Xenopus retina cells rely on intracellular nutrient stores, including glycogen1. Agathocleous et al. now demonstrate in vivo that proliferating progenitor cells of the developing retina rely on aerobic glycolysis (rather than on oxidative phosphorylation), which converts glucose to lactate, to support their metabolic needs2. This occurs even in the presence of oxygen, despite the fact that, when oxygen is available, oxidative phosphorylation allows more ATP to be produced per mole of glucose than glycolysis alone (Fig. 1). Interestingly, this preference for aerobic glycolysis is regulated by glycogen-phosphorylase-mediated glycogen metabolism. Even when progenitor cells are forced to utilize oxidative phosphorylation to produce ATP, by treating developing embryos with a glycogen phosphorylase inhibitor (GPI)3, they continue to depend on glycolytic flux for proliferation and survival. Only after terminal differentiation to non-proliferating retinal cells do the cells switch to oxidative phosphorylation. This work demonstrates that normal proliferating embryonic tissues use aerobic glycolysis even when relying on intracellular nutrient stores.