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  4. Parkin functionally interacts with PGC-1 proportional to to preserve mitochondria and protect dopaminergic neurons
 
research article

Parkin functionally interacts with PGC-1 proportional to to preserve mitochondria and protect dopaminergic neurons

Zheng, Lu
•
Bernard-Marissal, Nathalie
•
Moullan, Norman
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2017
Human Molecular Genetics

To understand the cause of Parkinson's disease (PD), it is important to determine the functional interactions between factors linked to the disease. Parkin is associated with autosomal recessive early-onset PD, and controls the transcription of PGC-1a, a master regulator of mitochondrial biogenesis. These two factors functionally interact to regulate the turnover and quality of mitochondria, by increasing both mitophagic activity and mitochondria biogenesis. In cortical neurons, co- expressing PGC-1a and Parkin increases the number of mitochondria, enhances maximal respiration, and accelerates the recovery of the mitochondrial membrane potential following mitochondrial uncoupling. PGC-1a enhances Mfn2 transcription, but also leads to increased degradation of the Mfn2 protein, a key ubiquitylation target of Parkin on mitochondria. In vivo, Parkin has significant protective effects on the survival and function of nigral dopaminergic neurons in which the chronic expression of PGC1a is induced. Ultrastructural analysis shows that these two factors together control the density of mitochondria and their interaction with the endoplasmic reticulum. These results highlight the combined effects of Parkin and PGC- 1a in the maintenance of mitochondrial homeostasis in dopaminergic neurons. These two factors synergistically control the quality and function of mitochondria, which is important for the survival of neurons in Parkinson's disease.

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HMG_26_3_582.pdf

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http://purl.org/coar/version/c_970fb48d4fbd8a85

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