Publication Date:
2022-05-26
Description:
© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Chen, R.; Park, H. A.; Mnatsakanyan, N.; Niu, Y.; Licznerski, P.; Wu, J.; Miranda, P.; Graham, M.; Tang, J.; Boon, A. J. W.; Cossu, G.; Mandemakers, W.; Bonifati, V.; Smith, P. J. S.; Alavian, K. N.; Jonas, E. A. Parkinson's disease protein DJ-1 regulates ATP synthase protein components to increase neuronal process outgrowth. Cell Death & Disease, 10(6), (2019):469, doi:10.1038/s41419-019-1679-x.
Description:
Familial Parkinson’s disease (PD) protein DJ-1 mutations are linked to early onset PD. We have found that DJ-1 binds directly to the F1FO ATP synthase β subunit. DJ-1’s interaction with the β subunit decreased mitochondrial uncoupling and enhanced ATP production efficiency while in contrast mutations in DJ-1 or DJ-1 knockout increased mitochondrial uncoupling, and depolarized neuronal mitochondria. In mesencephalic DJ-1 KO cultures, there was a progressive loss of neuronal process extension. This was ameliorated by a pharmacological reagent, dexpramipexole, that binds to ATP synthase, closing a mitochondrial inner membrane leak and enhancing ATP synthase efficiency. ATP synthase c-subunit can form an uncoupling channel; we measured, therefore, ATP synthase F1 (β subunit) and c-subunit protein levels. We found that ATP synthase β subunit protein level in the DJ-1 KO neurons was approximately half that found in their wild-type counterparts, comprising a severe defect in ATP synthase stoichiometry and unmasking c-subunit. We suggest that DJ-1 enhances dopaminergic cell metabolism and growth by its regulation of ATP synthase protein components.
Description:
The research was supported by NIH (NS081746) to E.A.J., W.M. and V.B. are supported by the Stichting Parkinson Fonds (The Netherlands).
Repository Name:
Woods Hole Open Access Server
Type:
Article
