Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, UK.
NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle upon Tyne, England.
J Neuromuscul Dis. 2023;10(6):1111-1126. doi: 10.3233/JND-230099.
Myotonic dystrophy type 1 (DM1) is a dominant autosomal neuromuscular disorder caused by the inheritance of a CTG triplet repeat expansion in the Dystrophia Myotonica Protein Kinase (DMPK) gene. At present, no cure currently exists for DM1 disease.
This study investigates the effects of 12-week resistance exercise training on mitochondrial oxidative phosphorylation in skeletal muscle in a cohort of DM1 patients (n = 11, men) in comparison to control muscle with normal oxidative phosphorylation.
Immunofluorescence was used to assess protein levels of key respiratory chain subunits of complex I (CI) and complex IV (CIV), and markers of mitochondrial mass and cell membrane in individual myofibres sampled from muscle biopsies. Using control's skeletal muscle fibers population, we classified each patient's fibers as having normal, low or high levels of CI and CIV and compared the proportions of fibers before and after exercise training. The significance of changes observed between pre- and post-exercise within patients was estimated using a permutation test.
At baseline, DM1 patients present with significantly decreased mitochondrial mass, and isolated or combined CI and CIV deficiency. After resistance exercise training, in most patients a significant increase in mitochondrial mass was observed, and all patients showed a significant increase in CI and/or CIV protein levels. Moreover, improvements in mitochondrial mass were correlated with the one-repetition maximum strength evaluation.
Remarkably, 12-week resistance exercise training is sufficient to partially rescue mitochondrial dysfunction in DM1 patients, suggesting that the response to exercise is in part be due to changes in mitochondria.
肌强直性营养不良 1 型（DM1）是一种显性常染色体神经肌肉疾病，由肌强直性蛋白激酶（DMPK）基因中的 CTG 三核苷酸重复扩展引起。目前，DM1 疾病尚无治愈方法。
本研究比较了正常氧化磷酸化的对照肌肉，调查了 12 周抗阻运动训练对 DM1 患者（n=11，男性）骨骼肌中线粒体氧化磷酸化的影响。
免疫荧光法用于评估来自肌肉活检的单个肌纤维中复合物 I（CI）和复合物 IV（CIV）关键呼吸链亚基以及线粒体质量和细胞膜标志物的蛋白水平。使用对照骨骼肌纤维群体，我们将每个患者的纤维分类为具有正常、低或高水平的 CI 和 CIV，并比较了运动训练前后纤维的比例。使用置换检验估计患者内预运动和后运动之间观察到的变化的显著性。
在基线时，DM1 患者表现出线粒体质量显著降低，以及单独或联合的 CI 和 CIV 缺陷。经过抗阻运动训练后，大多数患者的线粒体质量显著增加，所有患者的 CI 和/或 CIV 蛋白水平均显著增加。此外，线粒体质量的改善与一次重复最大力量评估相关。
值得注意的是，12 周的抗阻运动训练足以部分挽救 DM1 患者的线粒体功能障碍，这表明对运动的反应部分归因于线粒体的变化。
