Format

Send to

Choose Destination
Autophagy. 2014 Aug;10(8):1476-7. doi: 10.4161/auto.29642. Epub 2014 Jun 27.

SREBF1 links lipogenesis to mitophagy and sporadic Parkinson disease.

Author information

1
MRC Centre for Developmental and Biomedical Genetics; Sheffield, UK; Department of Biomedical Science; University of Sheffield; Sheffield, UK.

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.

KEYWORDS:

Drosophila; FBXW7; Parkin; Parkinson disease; SREBF1; lipids

PMID:
24991824
PMCID:
PMC4203527
DOI:
10.4161/auto.29642
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Taylor & Francis Icon for PubMed Central
Loading ...
Support Center