Journal
EUROPEAN JOURNAL OF NEUROSCIENCE
Volume 43, Issue 10, Pages 1379-1388Publisher
WILEY
DOI: 10.1111/ejn.13216
Keywords
Akt; DJ-1; in vitro; mitochondrial function; phosphorylation
Categories
Funding
- National Natural Science Foundation of China [81202939, 81473376, 81202507, 81573636, 81573773, 30873335]
- Specialized Research Fund for the Doctoral Program of Higher Education of China [20120013120007]
- Beijing Natural Science Foundation [7142115]
- Fundamental Scientific Research Funds for Central Public Institute [2014RC03]
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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 50-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.
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