Mitochondrial ferritin protects SH-SY5Y cells against H2O2-induced oxidative stress and modulates α-synuclein expression

• Published in: Experimental neurology 2017-05, Vol.291, p.51-61
• Main Authors: Guan, Hongpeng, Yang, Hongkuan, Yang, Mingchun, Yanagisawa, Daijiro, Bellier, Jean-Pierre, Mori, Masaki, Takahata, Shogo, Nonaka, Takashi, Zhao, Shiguang, Tooyama, Ikuo
• Format: Article
• Language: English
• Subjects: Iron; Mitochondrial ferritin; Oxidative stress; Parkinson's disease; α-Synuclein
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2017.02.001

Mitochondrial ferritin (FtMt) is a type of ferritin that sequesters iron. Previous studies have shown that FtMt is expressed by dopaminergic neurons in the substantia nigra and that it may be involved in the pathology of Parkinson's disease. However, the functional roles of FtMt in dopaminergic neurons remain unclear. In this study, we investigated the function of FtMt in α-synuclein regulation and its antioxidant roles in dopaminergic cells using human dopaminergic neuroblastoma cells, SH-SY5Y. In physiological conditions, FtMt knockdown increased α-synuclein expression at the protein level but not at the mRNA level. By contrast, FtMt overexpression reduced α-synuclein expression at the protein level but not at the mRNA level. FtMt enhanced the iron levels in mitochondria but decreased the iron levels in the intracellular labile iron pool. We found that FeCl2 could abolish the effects of FtMt overexpression on α-synuclein expression. Under oxidative stress conditions induced by H2O2, we found that H2O2 treatment induced FtMt and α-synuclein expression at both the mRNA and protein levels in a dose-dependent manner. FtMt overexpression protected cells against oxidative stress and alleviated the enhanced α-synuclein expression induced by H2O2 at the posttranscriptional level. Our results indicate that FtMt modulates α-synuclein expression at the posttranscriptional level via iron regulation in physiological conditions. FtMt expression is enhanced under oxidative stress conditions, where FtMt protects cells against the oxidative stress as well as plays an important role in maintaining α-synuclein levels. •FtMt downregulates α-synuclein protein expression but not mRNA.•FtMt overexpression rescues human dopaminergic cells from oxidative stress by H2O2.•FtMt partially inhibits the increase in α-synuclein expression induced by H2O2.•FtMt regulates posttranscriptional α-synuclein expression via iron regulation.