Hexokinases link DJ-1 to the PINK1/parkin pathway.

ABSTRACT:

Background

Early onset Parkinson's disease is caused by variants in PINK1, parkin, and DJ-1. PINK1 and parkin operate in pathways that preserve mitochondrial integrity, but the function of DJ-1 and how it relates to PINK1 and parkin is poorly understood.

Methods

A series of unbiased high-content screens were used to analyze changes at the protein, RNA, and metabolite level in rodent brains lacking DJ-1. Results were validated using targeted approaches, and cellular assays were performed to probe the mechanisms involved.

Results

We find that in both rat and mouse brains, DJ-1 knockout results in an age-dependent accumulation of hexokinase 1 in the cytosol, away from its usual location at the mitochondria, with subsequent activation of the polyol pathway of glucose meta

SUBMITTER: Hauser DN 

PROVIDER: S-EPMC5622528 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature