Mitochondrial Ferritin Protects Hydrogen Peroxide-Induced Neuronal Cell Damage

作者：Guofen Gao, Nan Zhang, Yueqi Wang, Qiong Wu, Peng Yu, Zhenhua Shi, Xianglin Duan, Baolu Zhao, Wenshuang Wu, Yan-Zhong Chang · 发表于：Aging and Disease · 年份：2017 · DOI：10.14336/ad.2016.1108 · 被引用次数：45 · 研究领域：Iron Metabolism and Disorders、Trace Elements in Health、Hemoglobinopathies and Related Disorders

Oxidative stress and iron accumulation are tightly associated with neurodegenerative diseases. Mitochondrial ferritin (FtMt) is identified as an iron-storage protein located in the mitochondria, and its role in regulation of iron hemeostasis in neurodegenerative diseases has been reported. However, the role of FtMt in hydrogen peroxide (H 2 O 2 )-induced oxidative stress and iron accumulation in neuronal cells has not been studied. Here, we overexpressed FtMt in neuroblastoma SH-SY5Y cells and induced oxidative stress by treating with extracellular H 2 O 2 . We found that overexpression of FtMt significantly prevented cell death induced by H 2 O 2 , particularly the apoptosis-dependent cell death. The protective effects involved inhibiting the generation of cellular reactive oxygen species, sustaining mitochondrial membrane potential, maintaining the level of anti-apoptotic protein Bcl-2, and inhibiting the activation of pro-apoptotic protein caspase 3. We further explored the mechanism of these protective effects and found that FtMt expression markedly altered iron homeostasis of the H 2 O 2 treated cells as compared to that of controls. The FtMt overexpression significantly reduced cellular labile iron pool (LIP) and protected H 2 O 2 -induced elevation on LIP. While in H 2 O 2 treated SH-SY5Y cells, the increased iron uptake and reduced iron release, in correlation with levels of DMT1(-IRE) and ferroportin 1, resulted in heavy iron accumulation, the FtMt overexpressing c...