Imperial College London
Alternate

Dr Kambiz N. Alavian, PhD, SFHEA, FLS, FRSB

Faculty of Medicine, Department of Brain Sciences

Reader in Neuroscience
 
 
 
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Contact

 

+44 (0)20 7594 7006k.alavian Website

 
 
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Assistant

 

Mrs Hadeel Abdeen +44 (0)20 7594 7014

 
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Location

 

E507Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Chen:2019:10.1038/s41419-019-1679-x,
author = {Chen, R and Park, H-A and Mnatsakanyan, N and Niu, Y and Licznerski, P and Wu, J and Miranda, P and Graham, M and Tang, J and Boon, AJW and Cossu, G and Mandemakers, W and Bonifati, V and Smith, PJS and Alavian, KN and Jonas, EA},
doi = {10.1038/s41419-019-1679-x},
journal = {Cell Death and Disease},
title = {Parkinson's disease protein DJ-1 regulates ATP synthase protein components to increase neuronal process outgrowth},
url = {http://dx.doi.org/10.1038/s41419-019-1679-x},
volume = {10},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Familial Parkinson’s disease (PD) protein DJ-1 mutations are linked to early onset PD. We have found that DJ-1 bindsdirectly to the F1FO ATP synthase β subunit. DJ-1’s interaction with the β subunit decreased mitochondrial uncouplingand enhanced ATP production efficiency while in contrast mutations in DJ-1 or DJ-1 knockout increased mitochondrialuncoupling, and depolarized neuronal mitochondria. In mesencephalic DJ-1 KO cultures, there was a progressive lossof neuronal process extension. This was ameliorated by a pharmacological reagent, dexpramipexole, that binds to ATPsynthase, closing a mitochondrial inner membrane leak and enhancing ATP synthase efficiency. ATP synthase csubunit can form an uncoupling channel; we measured, therefore, ATP synthase F1 (β subunit) and c-subunit proteinlevels. We found that ATP synthase β subunit protein level in the DJ-1 KO neurons was approximately half that foundin 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 proteincomponents.
AU  - Chen,R
AU  - Park,H-A
AU  - Mnatsakanyan,N
AU  - Niu,Y
AU  - Licznerski,P
AU  - Wu,J
AU  - Miranda,P
AU  - Graham,M
AU  - Tang,J
AU  - Boon,AJW
AU  - Cossu,G
AU  - Mandemakers,W
AU  - Bonifati,V
AU  - Smith,PJS
AU  - Alavian,KN
AU  - Jonas,EA
DO  - 10.1038/s41419-019-1679-x
PY  - 2019///
SN  - 2041-4889
TI  - Parkinson's disease protein DJ-1 regulates ATP synthase protein components to increase neuronal process outgrowth
T2  - Cell Death and Disease
UR  - http://dx.doi.org/10.1038/s41419-019-1679-x
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000472436800005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/71718
VL  - 10
ER  -
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