Fructose-driven glycolysis supports anoxia resistance in the naked mole-rat
Fructose-driven glycolysis supports anoxia resistance in the naked mole-rat
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DOI：
10.1126/science.aab3896
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发表时间：
2017-04-21
期刊：
影响因子：
56.9
通讯作者：
Lewin, Gary R.
中科院分区：
文献类型：
--
作者：
Park, Thomas J.;Reznick, Jane;Lewin, Gary R.
非洲裸鼹鼠（Heterocephalus glaber）的社会和地下生活方式产生了缺氧生态位。在实验条件下，裸鼹鼠可以耐受数小时的极度缺氧，并在完全缺氧（缺氧）的情况下存活 18 分钟而没有明显损伤。在缺氧期间，裸鼹鼠会切换到由果糖推动的无氧代谢，果糖在大脑中积极积累并代谢为乳酸。 GLUT5 果糖转运蛋白的整体表达和高水平的酮己糖激酶被确定为果糖代谢的分子特征。裸鼹鼠组织中果糖驱动的糖酵解呼吸避免了通过磷酸果糖激酶对糖酵解的反馈抑制，从而支持了活力。糖酵解的代谢重新布线可以避免缺氧通常造成的致命影响，这种机制可以用来最大限度地减少人类疾病中的缺氧损害。
The African naked mole-rat's (Heterocephalus glaber) social and subterranean lifestyle generates a hypoxic niche. Under experimental conditions, naked mole-rats tolerate hours of extreme hypoxia and survive 18 minutes of total oxygen deprivation (anoxia) without apparent injury. During anoxia, the naked mole-rat switches to anaerobic metabolism fueled by fructose, which is actively accumulated and metabolized to lactate in the brain. Global expression of the GLUT5 fructose transporter and high levels of ketohexokinase were identified as molecular signatures of fructose metabolism. Fructose-driven glycolytic respiration in naked mole-rat tissues avoids feedback inhibition of glycolysis via phosphofructokinase, supporting viability. The metabolic rewiring of glycolysis can circumvent the normally lethal effects of oxygen deprivation, a mechanism that could be harnessed to minimize hypoxic damage in human disease.