NRF2 Regulates PINK1 Expression under Oxidative Stress Conditions.

Abstract

Mutations of the PTEN-induced putative kinase 1 (PINK1) gene are a cause of autosomal recessive forms of Parkinson's disease. Recent studies have revealed that PINK1 is an essential factor for controlling mitochondrial quality, and that it protects cells from oxidative stresses. Although there has been considerable progress in the elucidation of various aspects of PINK1 protein regulation such as activation, stability and degradation, the transcriptional regulation of PINK1 mRNA under stress conditions remains unclear. In this study, we found that nuclear factor (erythroid-derived 2)-like 2 (NRF2), an antioxidant transcription factor, regulates PINK1 expression under oxidative stress conditions. Damaged mitochondria arising from stress conditions induced NRF2-dependent transcription of the PINK1 gene through production of reactive oxygen species (ROS). Either an ROS scavenger or forced expression of KEAP1, a potent inhibitory partner to NRF2, restricted PINK1 expression induced by activated NRF2. Transcriptionally up-regulated PINK1 diminished oxidative stress-associated cell death. The results indicate that PINK1 expression is positively regulated by NRF2 and that the NRF2-PINK1 signaling axis is deeply involved in cell survival.

• Authors: Hitoshi Murata, Hitoshi Takamatsu, Sulai Liu, Ken Kataoka, Nam-Ho Huh, Masakiyo Sakaguchi
• Journal: PloS one (PLoS One) Vol. 10 Issue 11 Pg. e0142438 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26555609 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-E2-Related Factor 2
• NFE2L2 protein, human
• RNA, Messenger
• Reactive Oxygen Species
• Protein Kinases
• PTEN-induced putative kinase

Topics

• Cell Line
• Humans
• NF-E2-Related Factor 2 (physiology)
• Oxidative Stress
• Protein Kinases (genetics)
• RNA, Messenger (genetics)
• Reactive Oxygen Species (metabolism)
• Signal Transduction
• Transcription, Genetic
• Up-Regulation