@article{58371e2ef6244641ae7ac4485ba746eb,
title = "Parkinson{\textquoteright}s disease protein DJ-1 regulates ATP synthase protein components to increase neuronal process outgrowth",
abstract = "Familial Parkinson{\textquoteright}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{\textquoteright}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.",
author = "Rongmin Chen and Park, {Han A.} and Nelli Mnatsakanyan and Yulong Niu and Pawel Licznerski and Jing Wu and Paige Miranda and Morven Graham and Jack Tang and Boon, {Agnita J.W.} and Giovanni Cossu and Wim Mandemakers and Vincenzo Bonifati and Smith, {Peter J.S.} and Alavian, {Kambiz N.} and Jonas, {Elizabeth A.}",
note = "Funding Information: 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). Funding Information: V.B. received research grants from the Stichting Parkinson Fonds (the Netherlands); the ZonMw (the Netherlands), under the aegis of the EU Joint Program–Neurodegenerative Disease Research (JPND); the Centre for Human Drug Research (Leiden, the Netherlands); and the Erasmus MC, Rotterdam. He receives compensation for serving as Section Editor of Current Neurology and Neuroscience Reports, and Editor-in-Chief of Parkinsonism and related disorders. He received honoraria from the International Parkinson and Movement Disorder Society, the Centre for Human Drug Research (the Netherlands), and the Sun Pharmaceutical Laboratories Limited (India). W.M. received research grants from the Stichting Parkinson Fonds (the Netherlands). E.A.J. receives compensation for serving as Associate Editor for the FASEB Journal. The other authors declare that they have no conflict of interest. Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = jun,
day = "1",
doi = "10.1038/s41419-019-1679-x",
language = "English (US)",
volume = "10",
journal = "Cell Death and Disease",
issn = "2041-4889",
publisher = "Nature Publishing Group",
number = "6",
}