Regulation of Mitochondrial Biogenesis and GLUT4 Expression by Exercise
Regulation of Mitochondrial Biogenesis and GLUT4 Expression by Exercise
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DOI：
10.1002/cphy.c100052
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发表时间：
2011-04-01
影响因子：
5.8
通讯作者：
Holloszy, John O.
中科院分区：
文献类型：
--
作者：
Holloszy, John O.
耐力运动训练可诱导骨骼肌线粒体和葡萄糖转运体GLUT 4亚型大量增加。在20世纪60年代发现运动导致肌肉线粒体增加后的很长一段时间里，在阐明相关机制方面没有进展。缺乏进展的原因是，对于编码线粒体蛋白的基因的表达如何协调调节一无所知。这种情况在发现控制基因编码线粒体蛋白质转录的转录因子后迅速改变，最重要的是，发现了过氧化物酶体增殖物-γ共激活因子-1 α（PGC-1 α）。这种转录辅激活因子结合并激活调节基因编码线粒体蛋白转录的转录因子。因此，PGC-1 α激活并协调线粒体生物发生。现在已知运动快速激活并诱导PGC-1 α表达增加。导致PGC-1 α激活和表达增加的运动产生的信号是细胞溶质Ca 2+的增加和ATP和磷酸肌酸（类似于P）的减少。Ca 2+通过激活CAMKII介导其作用，而类似于P的减少通过激活AMPK介导其作用。葡萄糖转运蛋白的GLUT 4同种型的表达通过相同的信号传导途径与线粒体生物合成平行调节。本文综述了运动对线粒体生物合成和GLUT 4表达的调节作用。本综述的一个主要组成部分涉及运动引起的线粒体和GLUT 4增加的生理和代谢后果。(C)2011年美国生理学会。Compr Physiol 1：921-940，2011年。
Endurance exercise training can induce large increases mitochondria and the GLUT4 isoform of the glucose transporter in skeletal muscle. For a long time after the discovery in the 1960s that exercise results in an increase in muscle mitochondria, there was no progress in elucidation of the mechanisms involved. The reason for this lack of progress was that nothing was known regarding how expression of the genes-encoding mitochondrial proteins is coordinately regulated. This situation changed rapidly after discovery of transcription factors that control transcription of genes-encoding mitochondrial proteins and, most importantly, the discovery of peroxisome proliferator-gamma coactivator-1 alpha (PGC-1 alpha). This transcription coactivator binds to and activates transcription factors that regulate transcription of genes-encoding mitochondrial proteins. Thus, PGC-1 alpha activates and coordinates mitochondrial biogenesis. It is now known that exercise rapidly activates and induces increased expression of PGC-1 alpha. The exercise-generated signals that lead to PGC-1 alpha activation and increased expression are the increases in cytosolic Ca2+ and decreases in ATP and creatine phosphate (similar to P). Ca2+ mediates its effect by activating CAMKII, while the decrease in similar to P mediates its effect via activation of AMPK. Expression of the GLUT4 isoform of the glucose transporter is regulated in parallel with mitochondrial biogenesis via the same signaling pathways. This review describes what is known regarding the regulation of mitochondrial biogenesis and GLUT4 expression by exercise. A major component of this review deals with the physiological and metabolic consequences of the exercise-induced increase in mitochondria and GLUT4. (C) 2011 American Physiological Society. Compr Physiol 1: 921-940, 2011.