Mitochondrial Dynamics of Proximal Tubular Epithelial Cells in Nephropathic Cystinosis

被引：20

作者：

De Rasmo, Domenico ^{[1
]}

Signorile, Anna ^{[2
]}

De Leo, Ester ^{[3
]}

Polishchuk, Elena V. ^{[4
]}

Ferretta, Anna ^{[1
]}

Raso, Roberto ^{[3
]}

Russo, Silvia ^{[2
]}

Polishchuk, Roman ^{[4
]}

Emma, Francesco ^{[5
]}

Bellomo, Francesco ^{[3
]}

机构：

[1] CNR, Inst Biomembranes Bioenerget & Mol Biotechnol IBI, I-70124 Bari, Italy

[2] Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, I-70124 Bari, Italy

[3] Bambino Gesu Childrens Hosp IRCCS, Genet & Rare Dis Res Div, Renal Dis Res Unit, I-00146 Rome, Italy

[4] Telethon Inst Genet & Med, I-80078 Pozzuoli, Italy

[5] Bambino Gesu Childrens Hosp IRCCS, Dept Pediat Subspecialties, Div Nephrol, I-00165 Rome, Italy

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2020年 / 21卷 / 01期

关键词：

Fanconi syndrome; nephropathic cystinosis; mitochondrial dynamics; cysteamine; mitochondrial fusion; mitochondrial fission; mitochondrial cristae; COMPLEX I; PROTEIN; MECHANISMS; DEGRADATION; APOPTOSIS; TRANSPORT; SUBUNITS; FISSION; DISEASE;

D O I：

10.3390/ijms21010192

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：11

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