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FOXO3 promoted mitophagy via nuclear retention induced by manganese chloride in SH-SY5Y cells

Abstract

Objectives: To evaluate the role of FOXO3 during the process of mitophagy induced by manganese chloride (MnCl2), mitochondrial dysfunction and mitophagy were detected before and after FOXO3 knowed down in SH-SY5Y cells. Method: Transmission Electron Microscopy (TEM), flow cytometry, Confocal Microscopy and Western Blot were used to detected mitochondrial ultrastructure and autophagy, levels of Ca2+, mitochondrial reactive oxygen species (ROS) and Mitochondrial Membrane Potential (MMP), autophagosomes and mitophagy marker proteins (p62, LC3-II/ LC3-I, Beclin-1, PINK1 and P- parkin), respectively. Results: After SH-SY5Y cells exposed to MnCl2, Levels of cytoplasmic Ca2+ and mitochondrial ROS increased but mitochondrial MMP decreased significantly compared to the control with dose- and time-dependent manner (p < 0.05), which indicated that MnCl2 can lead to mitochondria dysfunction. Under TEM, mitophagy and autolysosomes were observed. WB results also showed that mitophagy marker proteins including LC3-II/ LC3-I, Beclin-1, PINK1 and P- parkin except p62 increased with dose- and time-dependent manner, accompanied with FOXO3 nuclear retention, which indicated that MnCl2 can lead to mitophagy and FOXO3 nuclear translocation may be involved in the process. After FOXO3 knocked down, the inverse results of mitophagy and levels of mitochondrial ROS decreasing were observed, which showed that FOXO3 silenced could inhibit mitophagy and mitochondria dysfunction induced by MnCl2. Conclusions: Our results indicated that Mn could induce mitophagy by enhancing the nuclear FOXO3 retention, which might promote mitophagy induced by MnCl2.

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Publication details

The article was received on 26 Mar 2017, accepted on 19 Jun 2017 and first published on 19 Jun 2017


Article type: Paper
DOI: 10.1039/C7MT00085E
Citation: Metallomics, 2017, Accepted Manuscript
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    FOXO3 promoted mitophagy via nuclear retention induced by manganese chloride in SH-SY5Y cells

    D. Song, J. Ma, L. Chen, C. Guo, Y. Zhang, T. Chen, S. Zhang, Z. Zhu, L. Tian and P. Niu, Metallomics, 2017, Accepted Manuscript , DOI: 10.1039/C7MT00085E

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