Inhibition of autophagosome formation restores mitochondrial function in mucolipidosis II and III skin fibroblasts
Inhibition of autophagosome formation restores mitochondrial function in mucolipidosis II and III skin fibroblasts
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DOI：
10.1016/j.ymgme.2009.07.002
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发表时间：
2009-12-01
影响因子：
3.8
通讯作者：
Sakai, Norio
中科院分区：
文献类型：
--
作者：
Otomo, Takanobu;Higaki, Katsumi;Sakai, Norio
粘脂沉积症II型和III型是由N-乙酰葡糖胺-1-磷酸转移酶缺乏引起的进行性溶酶体贮积症，导致未消化的底物大量积聚在皮肤成纤维细胞的溶酶体（包涵体）中。在这项研究中，我们证明了在培养的成纤维细胞中自溶酶体的积累和p62和泛素蛋白水平的增加。这些自噬升高是温和的粘脂沉积症III相比，粘脂沉积症II。受影响细胞的线粒体结构被破坏，活性受损，自噬体形成抑制剂3-甲基腺嘌呤恢复了这些。这些结果首次显示了这种疾病中的自噬和线粒体功能障碍。(C)2009爱思唯尔公司所有权利
Mucolipidosis II and III are progressive lysosomal storage disorders caused by a deficiency of N-acetylglucosamine-1-phosphotransferase, leading to massive accumulation of undigested substrates in lysosomes (inclusion bodies) in skin fibroblast. In this study, we demonstrated accumulation of autolysosomes and increased levels of p62 and ubiquitin proteins in cultured fibroblasts. These autophagic elevations were milder in mucolipidosis III compared with mucolipidosis II. Mitochondrial structure was fragmented and activity was impaired in the affected cells, and 3-methyladenine, an inhibitor of autophagosome formation, restored these. These results show for the first time autophagic and mitochondrial dysfunctions in this disorder. (C) 2009 Elsevier Inc. All rights