Department of Biochemistry, Cell Biology and Microbiology, Mari State University, pl. Lenina 1, 424001 Yoshkar-Ola, Russia.
Laboratory of Mitochondrial Transport, Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Institutskaya 3, 142290 Pushchino, Russia.
Int J Mol Sci. 2020 Nov 19;21(22):8763. doi: 10.3390/ijms21228763.
Duchenne muscular dystrophy (DMD) is a severe hereditary disease caused by a lack of dystrophin, a protein essential for myocyte integrity. Mitochondrial dysfunction is reportedly responsible for DMD. This study examines the effect of glucocorticoid deflazacort on the functioning of the skeletal-muscle mitochondria of dystrophin-deficient mice and WT animals. Deflazacort administration was found to improve mitochondrial respiration of mice due to an increase in the level of ETC complexes (complexes III and IV and ATP synthase), which may contribute to the normalization of ATP levels in the skeletal muscle of animals. Deflazacort treatment improved the rate of Ca uniport in the skeletal muscle mitochondria of mice, presumably by affecting the subunit composition of the calcium uniporter of organelles. At the same time, deflazacort was found to reduce the resistance of skeletal mitochondria to MPT pore opening, which may be associated with a change in the level of ANT2 and CypD. In this case, deflazacort also affected the mitochondria of WT mice. The paper discusses the mechanisms underlying the effect of deflazacort on the functioning of mitochondria and contributing to the improvement of the muscular function of mice.
杜氏肌营养不良症（DMD）是一种由抗肌萎缩蛋白缺乏引起的严重遗传性疾病，该蛋白对肌细胞完整性至关重要。据报道，线粒体功能障碍是 DMD 的病因之一。本研究探讨了糖皮质激素地夫可特对肌营养不良症模型小鼠和 WT 动物骨骼肌线粒体功能的影响。研究发现，地夫可特的给药可通过增加电子传递链复合物（复合物 III 和 IV 以及 ATP 合酶）的水平来改善肌营养不良症模型小鼠的线粒体呼吸，这可能有助于肌营养不良症模型动物骨骼肌中 ATP 水平的正常化。地夫可特治疗可改善肌营养不良症模型小鼠骨骼肌线粒体的 Ca 单向转运速率，推测是通过影响细胞器钙单向转运体的亚基组成来实现的。同时，地夫可特还发现可降低骨骼肌线粒体对 MPT 孔开放的抵抗力，这可能与 ANT2 和 CypD 水平的变化有关。在这种情况下，地夫可特也影响了 WT 小鼠的线粒体。本文讨论了地夫可特对线粒体功能的影响的作用机制，并有助于改善肌营养不良症模型小鼠的肌肉功能。
