The impact of exercise on mitochondrial dynamics and the role of Drp1 in exercise performance and training adaptations in skeletal muscle
The impact of exercise on mitochondrial dynamics and the role of Drp1 in exercise performance and training adaptations in skeletal muscle
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DOI：
10.1016/j.molmet.2018.11.012
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发表时间：
2019-03-01
影响因子：
8.1
通讯作者：
Hevener, Andrea L.
中科院分区：
文献类型：
--
作者：
Moore, Timothy M.;Zhou, Zhenqi;Hevener, Andrea L.
目的：线粒体是主要负责产生能量的细胞器，最近的证据表明，线粒体的大小、形状、位置和数量都会随着能源供需的波动而发生变化。我们测试了急性和慢性运动对线粒体动力学信号的影响，并确定了线粒体分裂调节因子Dynamin Related Protein(DRP)1对运动成绩和肌肉对训练适应的影响。方法：对野生型和肌肉特异性Drp1杂合子(mDrp1(+/-))小鼠，以及血糖紊乱(DG)和血糖正常的健康男性(对照组)进行急慢性运动。结果：耐力运动影响线粒体生命周期的方方面面，即分裂-融合、生物发生和有丝分裂。急性运动后Dnm1L基因表达和Drp1(Ser616)磷酸化显著增加，运动后恢复至运动前水平。Dnm1L的表达与已知调节线粒体新陈代谢和运动适应的转录本密切相关。运动增加了健康对照组和DG受试者骨骼肌中DNM1L的表达，尽管DG的肌肉DNM1L表达在基线水平下降了15%(P=0.01)。为了进一步探讨Dnm1L的作用，我们训练了雄性mDrp1(+/-)小鼠，发现Drp1缺乏降低了肌肉耐力和跑步成绩，并改变了肌肉对运动训练的适应。结论：我们的发现强调了线粒体动力学，特别是Drp1信号，在调节运动表现和对耐力运动训练的适应中的重要性。(C)2018年作者。由Elsevier GmbH出版。
Objective: Mitochondria are organelles primarily responsible for energy production, and recent evidence indicates that alterations in size, shape, location, and quantity occur in response to fluctuations in energy supply and demand. We tested the impact of acute and chronic exercise on mitochondrial dynamics signaling and determined the impact of the mitochondrial fission regulator Dynamin related protein (Drp) 1 on exercise performance and muscle adaptations to training.Methods: Wildtype and muscle-specific Drp1 heterozygote (mDrp1(+/-)) mice, as well as dysglycemic (DG) and healthy normoglycemic men (control) performed acute and chronic exercise. The Hybrid Mouse Diversity Panel, including 100 murine strains of recombinant inbred mice, was used to identify muscle Dnm1L (encodes Drp1)-gene relationships.Results: Endurance exercise impacted all aspects of the mitochondrial life cycle, i.e. fission-fusion, biogenesis, and mitophagy. Dnm1L gene expression and Drp1(Ser616) phosphorylation were markedly increased by acute exercise and declined to baseline during post-exercise recovery. Dnm1L expression was strongly associated with transcripts known to regulate mitochondrial metabolism and adaptations to exercise. Exercise increased the expression of DNM1L in skeletal muscle of healthy control and DG subjects, despite a 15% down arrow(P = 0.01) in muscle DNM1L expression in DG at baseline. To interrogate the role of Dnm1L further, we exercise trained male mDrp1(+/-) mice and found that Drp1 deficiency reduced muscle endurance and running performance, and altered muscle adaptations in response to exercise training.Conclusion: Our findings highlight the importance of mitochondrial dynamics, specifically Drp1 signaling, in the regulation of exercise performance and adaptations to endurance exercise training. (C) 2018 The Authors. Published by Elsevier GmbH.