Department of Histology, Microbiology & Medical Biotechnology, University of Padova, Padova, Italy.
Autophagy. 2011 Apr;7(4):426-8. doi: 10.4161/auto.7.4.14392.
Collagen VI is an extracellular matrix protein forming a microfibrillar network in the endomysium of skeletal muscles. In humans, mutations in any of the three genes coding for collagen VI cause several skeletal muscle diseases, including Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD). Collagen VI null (Col6a1(-/-)) mice display a myopathic phenotype resembling that of BM and UCMD patients. Muscles lacking collagen VI are characterized by the presence of dilated sarcoplasmic reticulum and dysfunctional mitochondria, which triggers apoptosis and leads to muscle wasting. We have found that accumulation of abnormal organelles is due to an impairment of autophagy. Reactivation of the autophagic flux by either nutritional approaches or by pharmacological and genetics tools removes dysfunctional organelles and greatly ameliorates the dystrophic phenotype.
胶原 VI 是一种细胞外基质蛋白，在骨骼肌的肌内膜中形成微纤维网络。在人类中，编码胶原 VI 的三个基因中的任何一个突变都会导致几种骨骼肌疾病，包括 Bethlem 肌病 (BM) 和 Ullrich 先天性肌营养不良症 (UCMD)。胶原 VI 缺失 (Col6a1(-/-)) 小鼠表现出类似于 BM 和 UCMD 患者的肌病表型。缺乏胶原 VI 的肌肉的特征是存在扩张的肌浆网和功能失调的线粒体，这会触发细胞凋亡并导致肌肉萎缩。我们发现，异常细胞器的积累是由于自噬受损所致。通过营养方法或药理学和遗传学工具重新激活自噬流可以去除功能失调的细胞器，并极大地改善肌营养不良表型。
