Ivatt, R. M. and Whitworth, A. J. (2014) SREBF1 links lipogenesis to mitophagy and sporadic Parkinson disease. Autophagy, 10 (8). pp. 1476-1477. ISSN 1554-8627
Abstract
Mitochondrial quality control has an impact on many diseases, but intense research has focused on the action of 2 genes linked to heritable forms of Parkinson disease (PD), PINK1 and PARK2/parkin, which act in a common pathway to promote mitophagy. However, criticism has been raised that little evidence links this mechanism to sporadic PD. To gain a greater insight into the mechanisms of PINK1-PARK2 mediated mitophagy, we undertook a genome-wide RNAi screen in Drosophila and human cell models. Strikingly, we discovered several components of the lipogenesis pathway, including SREBF1, playing a conserved role in mitophagy. Our results suggest that lipids influence the stabilization of PINK1 during the initiation of mitophagy. Importantly, SREBF1 has previously been identified as a risk locus for sporadic PD, and thus implicates aberrant mitophagy as contributing to sporadic PD. Our findings suggest a role for lipid synthesis in PINK1-PARK2 mediated mitophagy, and propose a mechanistic link between familial and sporadic PD, supporting a common etiology.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2014 Landes Bioscience This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. https://creativecommons.org/licenses/by-nc/3.0/ |
Keywords: | SREBF1; Parkin; FBXW7; Parkinson disease; lipids; Drosophila |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 30 Nov 2016 12:14 |
Last Modified: | 30 Nov 2016 12:26 |
Published Version: | http://dx.doi.org/10.4161/auto.29642 |
Status: | Published |
Publisher: | Taylor & Francis: STM, Behavioural Science and Public Health Titles |
Refereed: | Yes |
Identification Number: | 10.4161/auto.29642 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:108580 |
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