Cathepsin-mediated regulation of autophagy in saposin C deficiency

被引：50

作者：

Tatti, Massimo ^{[1
]}

Motta, Marialetizia ^{[1
,2
]}

Di Bartolomeo, Sabrina ^{[3
]}

Cianfanelli, Valentina ^{[3
]}

Salvioli, Rosa ^{[1
]}

机构：

[1] Ist Super Sanita, Dept Haematol Oncol & Mol Med, I-00161 Rome, Italy

[2] Univ Roma La Sapienza, Dept Mol Med, San Camillo Forlanini Hosp, Rome, Italy

[3] Univ Roma Tor Vergata, Dept Biol, Dulbecco Telethon Inst, I-00173 Rome, Italy

来源：

AUTOPHAGY | 2013年 / 9卷 / 02期

关键词：

Gaucher disease; saposin C deficiency; glucosylceramidase deficiency; lysosomal storage disorders; glucosylceramide; autophagy; cathepsins; overexpression; autophagic lysosome reformation;

D O I：

10.4161/auto.22557

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Saposin C deficiency, a rare variant form of Gaucher disease, is due to mutations in the prosaposin gene (PSAP) affecting saposin C expression and/or function. We previously reported that saposin C mutations affecting one cysteine residue result in autophagy dysfunction. We further demonstrated that the accumulation of autophagosomes, observed in saposin C-deficient fibroblasts, is due to an impairment of autolysosome degradation, partially caused by the reduced amount and enzymatic activity of CTSB (cathepsin B) and CTSD (cathepsin D). The restoration of both proteases in pathological fibroblasts results in almost completely recovery of autophagic flux and lysosome homeostasis.

引用

页码：241 / 243

页数：3