Affiliations: Department of Neurobiology, Capital Medical University, Center of Parkinson’s Disease, Beijing Institute for Brain Disorders, Beijing Center of Neural Regeneration and Repair, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing, China
Correspondence:
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Correspondence to: Hui Yang, MD, Professor, Center of Parkinson’s Disease, Beijing Institute of Brain Disorders, Capital Medical University, Beijing Center of Neural Regeneration and Repair, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, 10 You an men Wai, Xitoutiao, Beijing 100069, China. Tel./Fax: +86 10 83950070; E-mails: huiyang@ccmu.edu.cn or huiyang0105@sina.com.
Abstract: PTEN induced putative kinase 1 (PINK1), also known as PARK6, is causally linked to familial Parkinsonism, and heterozygous loss of PINK1 is a risk factor for sporadic Parkinson’s disease. However, little is known about its physiological function. Its deficiency was shown to decrease dopamine without significant loss of dopaminergic neurons. We investigated the mechanistic basis for this observation in the present study using dopaminergic MN9D cells. We found that PINK1 knockdown resulted in dopamine content to decrease with suppressed tyrosine hydroxylase expression in cells. Conversely, PINK1 overexpression increased tyrosine hydroxylase protein level. We also found that PINK1 deficiency blocked the nuclear translocation and activity of nuclear receptor-related 1, a transcription factor regulating tyrosine hydroxylase gene expression. These data suggest that PINK1 regulates tyrosine hydroxylase gene expression and dopamine content by modulating the transcriptional activity of nuclear receptor-related 1. Taken together, our results reveal a novel function of PINK1 in dopamine homeostasis.
