Increased sensitivity to mitochondrial permeability transition and myonuclear translocation of endonuclease G in atrophied muscle of physically active older humans
Increased sensitivity to mitochondrial permeability transition and myonuclear translocation of endonuclease G in atrophied muscle of physically active older humans
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DOI：
10.1096/fj.13-242750
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发表时间：
2014-04-01
期刊：
影响因子：
4.8
通讯作者：
Hepple, Russell T.
中科院分区：
文献类型：
--
作者：
Gouspillou, Gilles;Sgarioto, Nicolas;Hepple, Russell T.
线粒体功能障碍与骨骼肌萎缩和衰老功能障碍有关，这有力地支持了久坐啮齿动物模型中线粒体介导的细胞凋亡增加。这是否适用于老年人的肌肉尚不清楚，也不清楚这些变化是否由久坐行为引起。因此，我们检查了从健康的体力活动的年轻人（23.7 +/- 2.7岁;平均值+/- sd）和老年人（71.2 +/- 4.9岁）的股外侧肌活检中获得的透化肌纤维的线粒体功能[呼吸，活性氧（ROS）排放和钙潴留能力（CRC）]。虽然线粒体活性氧和最大呼吸能力不受影响，受体控制率降低了18%，与老化，表明轻度解偶联的氧化磷酸化。CRC随着年龄的增长减少了50%，表明线粒体通透性转换孔（mPTP）对细胞凋亡的敏感性。与mPTP致敏一致，老年肌肉显示出3倍以上的核酸内切酶G（线粒体促凋亡因子）阳性肌细胞核。老年肌肉也有较低的线粒体吞噬电位，基于帕金的电压依赖性阴离子通道（VDAC）蛋白比例减少43%。总的来说，这些结果表明，线粒体介导的凋亡信号在老年人肌肉中增加，并表明具有过度凋亡敏感性的功能障碍线粒体的积累是由于线粒体自噬受损。Gouspillou，G.，Sgarioto，N.，Kapchinsky，S.，Purves-Smith，F.，诺里斯，B，皮翁角H、Barbat-Artigas，S.，Lemieux，F.，泰瓦萨洛，T.，Morais，J. A.，Aubertin-Leheudre，M.，赫普尔河T.在体力活动的老年人萎缩的肌肉中，对线粒体通透性转换和核酸内切酶G的肌内转位的敏感性增加。
Mitochondrial dysfunction is implicated in skeletal muscle atrophy and dysfunction with aging, with strong support for an increased mitochondrial-mediated apoptosis in sedentary rodent models. Whether this applies to aged human muscle is unknown, nor is it clear whether these changes are caused by sedentary behavior. Thus, we examined mitochondrial function [respiration, reactive oxygen species (ROS) emission, and calcium retention capacity (CRC)] in permeabilized myofibers obtained from vastus lateralis muscle biopsies of healthy physically active young (23.7 +/- 2.7 yr; mean +/- sd) and older (71.2 +/- 4.9 yr) men. Although mitochondrial ROS and maximal respiratory capacity were unaffected, the acceptor control ratio was reduced by 18% with aging, suggesting mild uncoupling of oxidative phosphorylation. CRC was reduced by 50% with aging, indicating sensitization of the mitochondrial permeability transition pore (mPTP) to apoptosis. Consistent with the mPTP sensitization, older muscles showed a 3-fold greater fraction of endonuclease G (a mitochondrial proapoptotic factor)-positive myonuclei. Aged muscles also had lower mitophagic potential, based on a 43% reduction in Parkin to the voltage-dependent anion channel (VDAC) protein ratio. Collectively, these results show that mitochondrial-mediated apoptotic signaling is increased in older human muscle and suggest that accumulation of dysfunctional mitochondria with exaggerated apoptotic sensitivity is due to impaired mitophagy.-Gouspillou, G., Sgarioto, N., Kapchinsky, S., Purves-Smith, F., Norris, B., Pion, C. H., Barbat-Artigas, S., Lemieux, F., Taivassalo, T., Morais, J. A., Aubertin-Leheudre, M., Hepple, R. T. Increased sensitivity to mitochondrial permeability transition and myonuclear translocation of endonuclease G in atrophied muscle of physically active older humans.