Overexpression of DJ-1/PARK7, the Parkinson's disease-related protein, improves mitochondrial function via Akt phosphorylation on threonine 308 in dopaminergic neuron-like cells
Overexpression of DJ-1/PARK7, the Parkinson's disease-related protein, improves mitochondrial function via Akt phosphorylation on threonine 308 in dopaminergic neuron-like cells
复制标题
帕金森病相关蛋白 DJ-1/PARK7 的过度表达通过 Akt 磷酸化多巴胺能神经元样细胞中的苏氨酸 308 来改善线粒体功能
DOI：
10.1111/ejn.13216
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发表时间：
2016
影响因子：
3.4
通讯作者：
Nai-Hong Chen
中科院分区：
文献类型：
--
作者：
Yi Zhang;Xiao-Gang Gong;Zhen-Zhen Wang;Hong-Mei Sun;Zhen-Yu Guo;Jing-Hong Hu;Ling Ma;Ping Li;Nai-Hong Chen
DJ‐1/PARK7, the Parkinson's disease‐related protein, plays an important role in mitochondrial function. However, the mechanisms by which DJ‐1 affects mitochondrial function are not fully understood. Akt is a promoter of neuron survival and is partly involved in the neurodegenerative process. This research aimed at investigating a possible relationship between DJ‐1 and Akt signalling in regulating mitochondrial function in the dopaminergic neuron‐like cells SH‐SY5Y and PC‐12. Overexpression of DJ‐1 was firstly validated at both the transcriptional and translational levels after transit transfection with plasmid pcDNA3‐Flag‐DJ‐1. Confocal fluorescence microscopy demonstrated that overexpression of DJ‐1 increased the mitochondrial mass, but did not disrupt the mitochondrial morphology. In addition, mitochondrial complex I activity was raised in DJ‐1‐overexpressing cells, and this rise occurred with an increase in cellular adenosine 5′‐triphosphate content. Moreover, immunoblotting demonstrated that the levels of phosphoinositide 3‐kinase and the total Akt were not altered in DJ‐1‐overexpressing cells, and nor was the Akt phosphorylation on serine 473 changed. By contrast, Akt phosphorylation on threonine 308 was significantly augmented by overexpression of DJ‐1, and the expression of glycogen synthase kinase‐3beta, a downstream effector of Akt, was suppressed. In summary, these results suggest that overexpression of DJ‐1 improves the mitochondrial function, at least in part, through a mechanism involving Akt phosphorylation on threonine 308.
