Format

Send to

Choose Destination
Autophagy. 2010 Oct;6(7):971-3. doi: 10.4161/auto.6.7.13099. Epub 2010 Oct 21.

Abnormal mitochondrial autophagy in nephropathic cystinosis.

Author information

1
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA. poonams@stanford.edu

Abstract

Cystinosis, which is characterized by lysosomal accumulation of cystine in many tissues, was the first known storage disorder caused by defective metabolite export from the lysosome. The molecular and cellular mechanisms underlying nephropathic cystinosis, the most severe form, which exhibits generalized proximal tubular dysfunction and progressive renal failure, remain largely unknown. We used renal proximal tubular epithelial (RPTE) cells and fibroblasts from patients with three clinical variants of cystinosis: nephropathic, intermediate and ocular to explore the specific injury mechanism in nephropathic cystinosis. We demonstrate enhanced autophagy of mitochondria, increase in apoptosis and mitochondrial dysfunction in the nephropathic cystinosis phenotype. Furthermore, specific inhibition of autophagy results in significant attenuation of cell death in nephropathic cystinosis. This study provides ultrastructural and functional evidence of abnormal mitochondrial autophagy in nephropathic cystinosis, which may contribute to renal Fanconi syndrome and progressive renal injury.

PMID:
20729635
PMCID:
PMC3039743
DOI:
10.4161/auto.6.7.13099
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Taylor & Francis Icon for PubMed Central
Loading ...
Support Center