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dc.contributor.authorChen, Rongmin  Concept link
dc.contributor.authorPark, Han-A  Concept link
dc.contributor.authorMnatsakanyan, Nelli  Concept link
dc.contributor.authorNiu, Yulong  Concept link
dc.contributor.authorLicznerski, Pawel  Concept link
dc.contributor.authorWu, Jing  Concept link
dc.contributor.authorMiranda, Paige  Concept link
dc.contributor.authorGraham, Morven  Concept link
dc.contributor.authorTang, Jack  Concept link
dc.contributor.authorBoon, Agnita J. W.  Concept link
dc.contributor.authorCossu, Giovanni  Concept link
dc.contributor.authorMandemakers, Wim  Concept link
dc.contributor.authorBonifati, Vincenzo  Concept link
dc.contributor.authorSmith, Peter J. S.  Concept link
dc.contributor.authorAlavian, Kambiz N.  Concept link
dc.contributor.authorJonas, Elizabeth A.  Concept link
dc.date.accessioned2019-07-08T20:55:44Z
dc.date.available2019-07-08T20:55:44Z
dc.date.issued2019-06-13
dc.identifier.citationChen, 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.urihttps://hdl.handle.net/1912/24336
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.abstractFamilial 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.sponsorshipThe 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.publisherSpringer Natureen_US
dc.relation.urihttp://doi.org/10.1038/s41419-019-1679-x
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleParkinson's disease protein DJ-1 regulates ATP synthase protein components to increase neuronal process outgrowthen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41419-019-1679-x


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International