Parkinson's disease protein DJ-1 regulates ATP synthase protein components to increase neuronal process outgrowth

dc.contributor.author Chen, Rongmin
dc.contributor.author Park, Han-A
dc.contributor.author Mnatsakanyan, Nelli
dc.contributor.author Niu, Yulong
dc.contributor.author Licznerski, Pawel
dc.contributor.author Wu, Jing
dc.contributor.author Miranda, Paige
dc.contributor.author Graham, Morven
dc.contributor.author Tang, Jack
dc.contributor.author Boon, Agnita J. W.
dc.contributor.author Cossu, Giovanni
dc.contributor.author Mandemakers, Wim
dc.contributor.author Bonifati, Vincenzo
dc.contributor.author Smith, Peter J. S.
dc.contributor.author Alavian, Kambiz N.
dc.contributor.author Jonas, Elizabeth A.
dc.date.accessioned 2019-07-08T20:55:44Z
dc.date.available 2019-07-08T20:55:44Z
dc.date.issued 2019-06-13
dc.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. en_US
dc.description.abstract 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. en_US
dc.description.sponsorship 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). en_US
dc.identifier.citation 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. (2019). Parkinson's disease protein DJ-1 regulates ATP synthase protein components to increase neuronal process outgrowth. Cell Death & Disease, 10(6), 469. en_US
dc.identifier.doi 10.1038/s41419-019-1679-x
dc.identifier.uri https://hdl.handle.net/1912/24336
dc.publisher Springer Nature en_US
dc.relation.uri http://doi.org/10.1038/s41419-019-1679-x
dc.rights Attribution 4.0 International *
dc.rights.uri http://creativecommons.org/licenses/by/4.0/ *
dc.title Parkinson's disease protein DJ-1 regulates ATP synthase protein components to increase neuronal process outgrowth en_US
dc.type Article en_US
dspace.entity.type Publication
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