A novel splicing variant of DJ-1 in Parkinson's disease induces mitochondrial dysfunction

Namjoon Cho, Jaegeon Joo, Sunkyung Choi, Bu Gyeong Kang, Andrew J. Lee, So Yeon Youn, Su Hyung Park, Eun Mi Kim, Eliezer Masliah, Yuji Ko, Sun Shin Cha, Inkyung Jung, Kee K. Kim

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Several studies have identified mutations in neuroprotective genes in a few cases of Parkinson's disease (PD); however, the role of alternative splicing changes in PD remains unelucidated. Based on the transcriptome analysis of substantia nigra (SN) tissues obtained from PD cases and age-matched healthy controls, we identified a novel alternative splicing variant of DJ-1, lacking exon 6 (DJ-1ΔE6), frequently detected in the SN of patients with PD. We found that the exon 6 skipping of DJ-1 induces mitochondrial dysfunction and impaired antioxidant capability. According to an in silico modeling study, the exon 6 skipping of DJ-1 disrupts the structural state suitable for the oxidation of the cysteine 106 residue that is a prerequisite for activating its neuroprotective roles. Our results suggest that change in DJ-1 alternative splicing may contribute to PD progression and provide an insight for studying PD etiology and its potential therapeutic targets.

Original languageEnglish
Article numbere14039
JournalHeliyon
Volume9
Issue number3
DOIs
StatePublished - Mar 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors

Keywords

  • Alternative splicing
  • DJ-1
  • Mitochondria
  • PARK7
  • Parkinson's disease

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