Parkin induced cell death upon mitochondrial depolarization is cell type dependent

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  • Parkin induced cell death upon mitochondrial depolarization is cell type dependent...
Gürler AKPINAR, Aylin KANLI, Murat KASAP
Department of Medical Biology/DEKART Proteomics Unit, Kocaeli University Medical School, Kocaeli, Turkey
Article Type
Orginal Article
Parkinson’s Disease, Parkin, Mitophagy, CCCP, SH-SY5Y


Background and aims: Parkin is a ubiquitin-protein ligase that ismutated in autosomal-juvenile Parkinsonism. Parkin’s interaction with depolarized mitochondriapromotes mitophagy and under normal conditions removal of damaged mitochondriahas a protective effect on cell survival. However, if the extent of mitochondrialdepolarization is overwhelming, then Parkin helps occurrence of large scale mitochondrialdepletion which results in cell death. In this study, the consequences of over expressingwild type Parkin in carbonyl cyanide m-chlorophenylhydrazone (CCCP)-treatedSH-SY5Y and HeLa cells were investigated. Materials and methods: For this purpose,cell lines expressing TetR protein was established. A wild type Parkin expressioncassette that could be induced following tetracycline treatment was introduced to thesecells. A HeLa-Parkin cell line that was previously established was also used. Results:The results demonstrated that HeLa cells responded to CCCP treatment like HEK293cells. Twenty five percent cell death occurred within 24 hr in the absence of Parkin while80% cell death occurred in the presence of Parkin. In contrast, treatment of uninducedSH-SY5Y cells with CCCP caused 60% cell death, and this level was not increased furtherby Parkin induction. Parkin expression in glucose-depleted medium also renderedHeLa cells but not the SH-SY5Y cells more sensitive to CCCP-induced cell death. Conclusion:Finally, Parkin expression protected SH-SY5Y cells from cell death inducedby tunicamycin treatment, which induces ER stress by blocking N-linked glycosylation,suggesting that Parkin protects these cells from this type of stress.

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