Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1α expression

被引:372
作者
Wright, David C. [1 ]
Han, Dong-Ho [1 ]
Garcia-Roves, Pablo M. [1 ]
Geiger, Paige C. [1 ]
Jones, Terry E. [1 ]
Holloszy, John O. [1 ]
机构
[1] Washington Univ, Sch Med, Sect Appl Physiol, Dept Med, St Louis, MO 63110 USA
关键词
D O I
10.1074/jbc.M606116200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Exercise results in rapid increases in expression of the transcription coactivator peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) and in mitochondrial biogenesis in skeletal muscle. PGC-1a regulates and coordinates mitochondrial biogenesis, and overexpression of PGC-1 alpha in muscle cells results in increases in mitochondrial content. In this context, it has been proposed that the increase in PGC-1 alpha protein expression mediates the exercise-induced increase in mitochondrial biogenesis. However, we found that mitochondrial proteins with a short half-life increase as rapidly as, or more rapidly than, PGC-1 alpha protein. This finding led us to hypothesize that activation, rather than increased expression, of PGC-1 alpha mediates the initial phase of the exercise-induced increase in mitochondria. In this study, we found that most of the PGC-1 alpha in resting skeletal muscle is in the cytosol. Exercise resulted in activation of p38 MAPK and movement of PGC-1 alpha into the nucleus. In support of our hypothesis, binding of the transcription factor nuclear respiratory factor 1 (NRF-1) to the cytochrome c promoter and NRF-2 to the cytochrome oxidase subunit 4 promoter increased in response to exercise prior to an increase in PGC-1 alpha protein. Furthermore, exercise-induced increases in the mRNAs of cytochrome c, delta-aminolevulinate synthase, and citrate synthase also occurred before an increase in PGC-1 protein. Thus, it appears that activation of PGC-1 alpha may mediate the initial phase of the exercise-induced adaptive increase in muscle mitochondria, whereas the subsequent increase in PGC-1 alpha protein sustains and enhances the increase in mitochondrial biogenesis.
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页码:194 / 199
页数:6
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