SREBF1 links lipogenesis to mitophagy and sporadic Parkinson disease
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 evid...
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| Format: | Online |
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Landes Bioscience
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203527/ |
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pubmed-4203527 |
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pubmed-42035272015-08-01 SREBF1 links lipogenesis to mitophagy and sporadic Parkinson disease Ivatt, Rachael M Whitworth, Alexander J Autophagic Punctum 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. Landes Bioscience 2014-08-01 2014-06-27 /pmc/articles/PMC4203527/ /pubmed/24991824 http://dx.doi.org/10.4161/auto.29642 Text en Copyright © 2014 Landes Bioscience http://creativecommons.org/licenses/by-nc/3.0/ 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. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Ivatt, Rachael M Whitworth, Alexander J |
| spellingShingle |
Ivatt, Rachael M Whitworth, Alexander J SREBF1 links lipogenesis to mitophagy and sporadic Parkinson disease |
| author_facet |
Ivatt, Rachael M Whitworth, Alexander J |
| author_sort |
Ivatt, Rachael M |
| title |
SREBF1 links lipogenesis to mitophagy and sporadic Parkinson disease |
| title_short |
SREBF1 links lipogenesis to mitophagy and sporadic Parkinson disease |
| title_full |
SREBF1 links lipogenesis to mitophagy and sporadic Parkinson disease |
| title_fullStr |
SREBF1 links lipogenesis to mitophagy and sporadic Parkinson disease |
| title_full_unstemmed |
SREBF1 links lipogenesis to mitophagy and sporadic Parkinson disease |
| title_sort |
srebf1 links lipogenesis to mitophagy and sporadic parkinson disease |
| description |
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. |
| publisher |
Landes Bioscience |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203527/ |
| _version_ |
1613146743235411968 |