DJ-1 is indispensable for the S-nitrosylation of Parkin, which maintains function of mitochondria.

Scientific Reports
Kentaro OzawaYasuo Uchiyama

Abstract

The DJ-1 gene, a causative gene for familial Parkinson's disease (PD), has been reported to have various functions, including transcriptional regulation, antioxidant response, and chaperone and protease functions; however, the molecular mechanism associated with the pathogenesis of PD remains elusive. To further explore the molecular function of DJ-1 in the pathogenesis of PD, we compared protein expression profiles in brain tissues from wild-type and DJ-1-deficient mice. Two-dimensional difference gel electrophoresis analysis and subsequent analysis using data mining methods revealed alterations in the expression of molecules associated with energy production. We demonstrated that DJ-1 deletion inhibited S-nitrosylation of endogenous Parkin as well as overexpressed Parkin in neuroblastoma cells and mouse brain tissues. Thus, we used genome editing to generate neuroblastoma cells with DJ-1 deletion or S-nitrosylated cysteine mutation in Parkin and demonstrated that these cells exhibited similar phenotypes characterized by enhancement of cell death under mitochondrial depolarization and dysfunction of mitochondria. Our data indicate that DJ-1 is required for the S-nitrosylation of Parkin, which positively affects mitochondrial f...Continue Reading

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Citations

Oct 18, 2020·Biomedicines·Maria EjmaGjumrakch Aliev
Nov 24, 2020·Oxidative Medicine and Cellular Longevity·Natalia Jimenez-Moreno, Jon D Lane
Feb 10, 2021·Redox Biology·Federica De LazzariMarco Bisaglia
Apr 6, 2021·Archives of Biochemistry and Biophysics·Esha SircarRajib Sengupta
May 8, 2021·Antioxidants & Redox Signaling·Tomohiro NakamuraStuart A Lipton
Jun 11, 2021·Biochemical Pharmacology·Fátima E Murillo-GonzálezGuillermo Elizondo
Jun 27, 2021·Progress in Neurobiology·Maoxin Huang, Shengdi Chen

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Methods Mentioned

BETA
ubiquitination
electrophoresis
transfection
flow cytometry
confocal microscopy
Assay
Protein Assay

Software Mentioned

NIH ImageJ
KeyMolnet
Protein Analysis Through Evolutionary Relationships ( PANTHER )

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