SREBF1 links lipogenesis to mitophagy and sporadic Parkinson disease.

TitleSREBF1 links lipogenesis to mitophagy and sporadic Parkinson disease.
Publication TypeJournal Article
Year of Publication2014
AuthorsIvatt, RM, Whitworth, AJ
Date Published2014 Aug
KeywordsAnimals, Drosophila melanogaster, Enzyme Stability, Humans, Lipogenesis, Mitochondria, Mitophagy, Models, Biological, Parkinson Disease, Protein Kinases, Sterol Regulatory Element Binding Protein 1, Ubiquitin-Protein Ligases

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.

Alternate JournalAutophagy
Citation Key10.4161/auto.29642
PubMed ID24991824
PubMed Central IDPMC4203527
Grant List089698 / / Wellcome Trust / United Kingdom
MC_G1000735 / / Medical Research Council / United Kingdom