Glycolysis-respiration relationships in a neuroblastoma cell line.
Glycolysis-respiration relationships in a neuroblastoma cell line.
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DOI：
10.1016/j.bbagen.2013.01.002
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发表时间：
2013-04
影响因子：
3
通讯作者：
Lu, Jianghua
中科院分区：
文献类型：
--
作者：
Swerdlow, Russell H.;Lezi, E.;Aires, Daniel;Lu, Jianghua
虽然一些相互的糖酵解-呼吸的关系是公认的，减少糖酵解通量和线粒体呼吸之间的关系还没有得到严格的特点。我们同时测量了SH-SY 5 Y神经母细胞瘤细胞在自由和限制糖酵解通量条件下的细胞外酸化率（ECAR）和耗氧率（OCR）。在能源需求量一定的条件下，ECAR和OCR值呈反比关系。除了观察到预期的克拉布特里效应（增加葡萄糖可用性提高ECAR并降低OCR）外，还记录了一种新的相互关系，其中通过葡萄糖剥夺或糖酵解抑制降低ECAR可增加OCR。用半乳糖取代葡萄糖，这降低了净糖酵解ATP产率而不阻断糖酵解通量，类似地降低了ECAR并增加了OCR。我们进一步确定了减少ECAR条件如何影响与能量传感和能量响应途径相关的蛋白质。ERK磷酸化、SIRT 1和HIF 1a减少，而AKT、p38和AMPK磷酸化增加。这些数据证明了一种新的细胞内糖酵解-呼吸效应，其中限制糖酵解通量增加线粒体呼吸。由于这种效应可用于操纵细胞生物能量基础设施，这种特殊的糖酵解-呼吸效应实际上可以为新的线粒体医学方法的发展提供信息。
Although some reciprocal glycolysis-respiration relationships are well recognized, the relationship between reduced glycolysis flux and mitochondrial respiration has not been critically characterized. We concomitantly measured the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) of SH-SY5Y neuroblastoma cells under free and restricted glycolysis flux conditions. Under conditions of fixed energy demand ECAR and OCR values showed a reciprocal relationship. In addition to observing an expected Crabtree effect in which increasing glucose availability raised the ECAR and reduced the OCR, a novel reciprocal relationship was documented in which reducing the ECAR via glucose deprivation or glycolysis inhibition increased the OCR. Substituting galactose for glucose, which reduces net glycolysis ATP yield without blocking glycolysis flux, similarly reduced the ECAR and increased the OCR. We further determined how reduced ECAR conditions affect proteins that associate with energy sensing and energy response pathways. ERK phosphorylation, SIRT1, and HIF1a decreased while AKT, p38, and AMPK phosphorylation increased. These data document a novel intracellular glycolysis-respiration effect in which restricting glycolysis flux increases mitochondrial respiration. Since this effect can be used to manipulate cell bioenergetic infrastructures, this particular glycolysis-respiration effect can practically inform the development of new mitochondrial medicine approaches.
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影响因子：
4.8
作者：
Hofhaus, G;Johns, DR;Chomyn, A
通讯作者：
Chomyn, A
影响因子：
4.4
作者：
Cantó C;Auwerx J
通讯作者：
Auwerx J
影响因子：
13.8
作者：
Mendoza, Michelle C.;Er, E. Emrah;Blenis, John
通讯作者：
Blenis, John
影响因子：
7.4
作者：
Dranka BP;Benavides GA;Diers AR;Giordano S;Zelickson BR;Reily C;Zou L;Chatham JC;Hill BG;Zhang J;Landar A;Darley-Usmar VM
通讯作者：
Darley-Usmar VM
影响因子：
4.1
作者：
Crabtree, HG
通讯作者：
Crabtree, HG