DJ-1 regulates mitochondrial gene expression during ischemia and reperfusion

Free Radic Biol Med. 2022 Nov 20;193(Pt 1):430-436. doi: 10.1016/j.freeradbiomed.2022.10.315. Epub 2022 Oct 28.

Abstract

The early-onset Parkinson's disease protein DJ-1 is a multifunctional protein that plays a protective role against ischemia and reperfusion (I/R) injury and oxidative stress. Despite lacking a canonical RNA-binding domain DJ-1 exhibits RNA-binding activity and multiple transcripts have been identified. However, no functional characterization has been provided to date. Here, we have investigated the DJ-1-interacting transcripts, as well as the role of DJ-1 RNA-binding activity during ischemia and reperfusion. Among the identified DJ-1-interacting transcripts, we have distinguished a significant enrichment of mRNAs encoding mitochondrial proteins. The effects of DJ-1 depletion on mitochondrial protein expression and mitochondrial morphology were investigated using a CRISPR/Cas9 generated DJ-1 knockout (DJ-1KO) cell model. DJ-1 depletion resulted in increased MTND2 protein expression in resting cells; however, after exposure to I/R, MTND2 levels were significantly reduced with respect to wild type cells. Increased mitochondrial fission was consistently found in DJ-1KO cells after I/R exposure. MTND2 transcript binding to DJ-1 was increased during ischemia. Our results indicate that the RNA-binding activity of DJ-1 shield mitochondrial transcripts from oxidative damage.

Keywords: DJ-1; Ischemia; Ischemia/reperfusion; Mitochondria; PARK7; RNA-Binding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genes, Mitochondrial*
  • Humans
  • Ischemia / metabolism
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Oxidative Stress / genetics
  • Protein Deglycase DJ-1 / genetics
  • Protein Deglycase DJ-1 / metabolism
  • RNA / metabolism
  • Reperfusion
  • Reperfusion Injury* / genetics
  • Reperfusion Injury* / metabolism

Substances

  • Protein Deglycase DJ-1
  • RNA
  • PARK7 protein, human