Sengupta Archya, Padhan Deepesh Kumar, Ganguly Ananya, Sen Malini
Division of Cancer Biology & Inflammatory Disorder, CSIR-Indian Institute of Chemical Biology, Kolkata, India.
Front Cell Dev Biol. 2021 Feb 11;9:627409. doi: 10.3389/fcell.2021.627409. eCollection 2021.
Mutations in the () gene are linked with a debilitating musculoskeletal disorder, termed progressive pseudorheumatoid dysplasia (PPRD). Yet, the functional significance of CCN6 in the musculoskeletal system remains unclear. Using zebrafish as a model organism, we demonstrated that zebrafish Ccn6 is present partly as a component of mitochondrial respiratory complexes in the skeletal muscle of zebrafish. Morpholino-mediated depletion of Ccn6 in the skeletal muscle leads to a significant reduction in mitochondrial respiratory complex assembly and activity, which correlates with loss of muscle mitochondrial abundance. These mitochondrial deficiencies are associated with notable architectural and functional anomalies in the zebrafish muscle. Taken together, our results indicate that Ccn6-mediated regulation of mitochondrial respiratory complex assembly/activity and mitochondrial integrity is important for the maintenance of skeletal muscle structure and function in zebrafish. Furthermore, this study suggests that defects related to mitochondrial respiratory complex assembly/activity and integrity could be an underlying cause of muscle weakness and a failed musculoskeletal system in PPRD.
（）基因的突变与一种使人虚弱的肌肉骨骼疾病相关，称为进行性假类风湿性发育不良（PPRD）。然而，CCN6在肌肉骨骼系统中的功能意义仍不清楚。我们以斑马鱼作为模式生物，证明斑马鱼Ccn6部分以线粒体呼吸复合体组分的形式存在于斑马鱼骨骼肌中。吗啉代介导的骨骼肌中Ccn6缺失导致线粒体呼吸复合体组装和活性显著降低，这与肌肉线粒体丰度的丧失相关。这些线粒体缺陷与斑马鱼肌肉中显著的结构和功能异常有关。综上所述，我们的结果表明，Ccn6介导的线粒体呼吸复合体组装/活性调节以及线粒体完整性对于维持斑马鱼骨骼肌结构和功能很重要。此外，本研究表明，与线粒体呼吸复合体组装/活性及完整性相关的缺陷可能是PPRD中肌肉无力和肌肉骨骼系统功能障碍的潜在原因。
