Autophagy is required for exercise training-induced skeletal muscle adaptation and improvement of physical performance
Autophagy is required for exercise training-induced skeletal muscle adaptation and improvement of physical performance
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DOI：
10.1096/fj.13-228486
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发表时间：
2013-10-01
期刊：
影响因子：
4.8
通讯作者：
Yan, Zhen
中科院分区：
文献类型：
--
作者：
Lira, Vitor A.;Okutsu, Mitsuharu;Yan, Zhen
病理和生理刺激，包括急性运动，激活自噬;然而，尚不清楚运动训练是否改变自噬的基础水平，以及自噬是否是骨骼肌适应训练所必需的。我们观察到更大的自噬通量（即，增加的LC 3-II/LC 3-I比率和LC 3-II水平以及减少的p62蛋白含量的组合表明自噬事件的较高起始和消退速率），自噬蛋白表达（即，Atg 6/Beclin 1，Atg 7和Atg 8/LC 3）和线粒体自噬蛋白Bnip 3在紧张性，氧化性肌肉中的表达，与小鼠混合纤维类型或主要糖酵解纤维的肌肉相比。长期自愿运行（4周）导致增加的基础自噬流量和自噬蛋白和Bnip 3的表达与线粒体生物合成在跖肌混合纤维类型。相反，运动训练促进了自噬蛋白的表达，而氧化比目鱼肌中的自噬通量和线粒体生物合成没有显著增加。我们还观察到增加的基础自噬通量和Bnip 3含量，而不增加自噬蛋白表达的久坐肌肉特异性Pgc-1转基因小鼠的跖肌，增强线粒体生物合成的遗传模型。这些发现表明，耐力运动训练诱导的基础自噬增加，包括线粒体自噬，只有在氧化表型增强的情况下才会发生。然而，自噬蛋白的表达主要取决于独立于氧化表型增强的收缩活性。关键自噬蛋白Atg 6杂合子的运动训练小鼠表现出基础自噬通量、线粒体含量和骨骼肌血管生成的减弱增加，沿着耐力改善受损。这些结果表明，增加的基础自噬是耐力运动训练诱导的骨骼肌适应和身体表现改善所必需的。Okutsu，M.，张，M.，格林，N. P.，莱克河C.的方法，Breen，D.美国，霍恩，K. L.，Yan，Z.自噬是运动训练诱导的骨骼肌适应和体能改善所必需的。
Pathological and physiological stimuli, including acute exercise, activate autophagy; however, it is unknown whether exercise training alters basal levels of autophagy and whether autophagy is required for skeletal muscle adaptation to training. We observed greater autophagy flux (i.e., a combination of increased LC3-II/LC3-I ratio and LC3-II levels and reduced p62 protein content indicating a higher rate of initiation and resolution of autophagic events), autophagy protein expression (i.e., Atg6/Beclin1, Atg7, and Atg8/LC3) and mitophagy protein Bnip3 expression in tonic, oxidative muscle compared to muscles of either mixed fiber types or of predominant glycolytic fibers in mice. Long-term voluntary running (4 wk) resulted in increased basal autophagy flux and expression of autophagy proteins and Bnip3 in parallel to mitochondrial biogenesis in plantaris muscle with mixed fiber types. Conversely, exercise training promoted autophagy protein expression with no significant increases of autophagy flux and mitochondrial biogenesis in the oxidative soleus muscle. We also observed increased basal autophagy flux and Bnip3 content without increases in autophagy protein expression in the plantaris muscle of sedentary muscle-specific Pgc-1 transgenic mice, a genetic model of augmented mitochondrial biogenesis. These findings reveal that endurance exercise training-induced increases in basal autophagy, including mitophagy, only take place if an enhanced oxidative phenotype is achieved. However, autophagy protein expression is mainly dictated by contractile activity independently of enhancements in oxidative phenotype. Exercise-trained mice heterozygous for the critical autophagy protein Atg6 showed attenuated increases of basal autophagy flux, mitochondrial content, and angiogenesis in skeletal muscle, along with impaired improvement of endurance capacity. These results demonstrate that increased basal autophagy is required for endurance exercise training-induced skeletal muscle adaptation and improvement of physical performance.Lira, V. A., Okutsu, M., Zhang, M., Greene, N. P., Laker, R. C., Breen, D. S., Hoehn, K. L., Yan, Z. Autophagy is required for exercise training-induced skeletal muscle adaptation and improvement of physical performance.