Proteomic identification of a stress protein, mortalin/mthsp70/GRP75: relevance to Parkinson disease.

Published

Journal Article

Functional impairment of mitochondria and proteasomes and increased oxidative damage comprise the main pathological phenotypes of Parkinson disease (PD). Using an unbiased quantitative proteomic approach, we compared nigral mitochondrial proteins of PD patients with those from age-matched controls. 119 of 842 identified proteins displayed significant differences in their relative abundance (increase/decrease) between the two groups. We confirmed that one of these, mortalin (mthsp70/GRP75, a mitochondrial stress protein), is substantially decreased in PD brains as well as in a cellular model of PD. In addition, nine candidate mortalin-binding partners were identified as potential mediators of PD pathology. Manipulations of mortalin level in dopaminergic neurons resulted in significant changes in sensitivity to PD phenotypes via pathways involving mitochondrial and proteasomal function as well as oxidative stress.

Full Text

Duke Authors

Cited Authors

  • Jin, J; Hulette, C; Wang, Y; Zhang, T; Pan, C; Wadhwa, R; Zhang, J

Published Date

  • July 2006

Published In

Volume / Issue

  • 5 / 7

Start / End Page

  • 1193 - 1204

PubMed ID

  • 16565515

Pubmed Central ID

  • 16565515

Electronic International Standard Serial Number (EISSN)

  • 1535-9484

International Standard Serial Number (ISSN)

  • 1535-9476

Digital Object Identifier (DOI)

  • 10.1074/mcp.m500382-mcp200

Language

  • eng