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Mitochondrial Dynamics of Proximal Tubular Epithelial Cells in Nephropathic Cystinosis.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2019 Dec 26; Vol. 21 (1). Date of Electronic Publication: 2019 Dec 26. - Publication Year :
- 2019
-
Abstract
- Nephropathic cystinosis is a rare lysosomal storage disorder caused by mutations in CTNS gene leading to Fanconi syndrome. Independent studies reported defective clearance of damaged mitochondria and mitochondrial fragmentation in cystinosis. Proteins involved in the mitochondrial dynamics and the mitochondrial ultrastructure were analyzed in CTNS -/- cells treated with cysteamine, the only drug currently used in the therapy for cystinosis but ineffective to treat Fanconi syndrome. CTNS -/- cells showed an overexpression of parkin associated with deregulation of ubiquitination of mitofusin 2 and fission 1 proteins, an altered proteolytic processing of optic atrophy 1 (OPA1), and a decreased OPA1 oligomerization. According to molecular findings, the analysis of electron microscopy images showed a decrease of mitochondrial cristae number and an increase of cristae lumen and cristae junction width. Cysteamine treatment restored the fission 1 ubiquitination, the mitochondrial size, number and lumen of cristae, but had no effect on cristae junction width, making CTNS -/- tubular cells more susceptible to apoptotic stimuli.
- Subjects :
- Cells, Cultured
Cystinosis metabolism
Epithelial Cells cytology
Epithelial Cells drug effects
Epithelial Cells metabolism
GTP Phosphohydrolases metabolism
Humans
Kidney Tubules, Proximal cytology
Kidney Tubules, Proximal drug effects
Kidney Tubules, Proximal metabolism
Membrane Proteins metabolism
Mitochondria drug effects
Mitochondrial Dynamics drug effects
Mitochondrial Proteins metabolism
Ubiquitin-Protein Ligases metabolism
Ubiquitination
Amino Acid Transport Systems, Neutral genetics
Cysteamine pharmacology
Cystinosis genetics
Mitochondria metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 21
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 31888107
- Full Text :
- https://doi.org/10.3390/ijms21010192