Alterations in the mitochondrial proteome of neuroblastoma cells 2 in response to complex 1 inhibition

BURTÉ, F., DE GIROLAMO, L.A., HARGREAVES, A.J. and BILLETT, E.E., 2011. Alterations in the mitochondrial proteome of neuroblastoma cells 2 in response to complex 1 inhibition. Journal of Proteome Research, 10 (4). ISSN 1535-3893

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Abstract

Increasing evidence points to mitochondrial dysfunction in Parkinson's disease (PD) associated with complex I dysfunction, but the exact pathways which lead to cell death have not been resolved. 2D-gel electrophoresis profiles of isolated mitochondria from neuroblastoma cells treated with subcytotoxic concentrations of l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP), a well-characterized complex I inhibitor, were assessed to identify associated targets. Up to 27 differentially expressed proteins were observed, of which 16 were identified using peptide mass fingerprinting. Changes in protein levels were validated by immunoprobing ID blots, confirming increases in heat shock cognate 71 kDa (Hsc70), 60 kDa heat shock protein (Hsp60), fumarase, glutamate oxaloacetate transaminase 2, ATP synthase subunit d, and voltage-dependent anion-channel 1 (VDACl). Immunoprobing of 2D blots revealed isoform changes in Hsc70, Hsp60, and VDACl. Subcytoxic concentrations of MPTP modulated a host of mitochondrial proteins including chaperones, metabolic enzymes, oxidative phosphorylation-related proteins, an inner mitochondrial protein (mitofilin), and an outer mitochondrial membrane protein (VDACl). Early changes in chaperones suggest a regulated link between complex 1 inhibition and protein folding. VDACl, a multifunctional protein, may have a key role in signaling between mitochondria and the rest of the cell prior to cell death. Our work provides new important information of relevance to PD.

Item Type: Journal article
Description: Reprinted with permsision from BURTÉ, F., DE GIROLAMO, L.A., HARGREAVES, A.J. and BILLETT, E.E., 2011. Alterations in the mitochondrial proteome of neuroblastoma cells 2 in response to complex 1 inhibition. Journal of Proteome Research, 10 (4), pp. 1974–1986. Copyright 2011 American Chemical Society.
Publication Title: Journal of Proteome Research
Creators: Burté, F., De Girolamo, L.A., Hargreaves, A.J. and Billett, E.E.
Publisher: ACS Publications
Place of Publication: Washington DC
Date: 2011
Volume: 10
Number: 4
ISSN: 1535-3893
Identifiers:
NumberType
10.1021/pr101211kDOI
Rights: Copyright © 2011 American Chemical Society
Divisions: Schools > School of Science and Technology
Depositing User: EPrints Services
Date Added: 09 Oct 2015 10:16
Last Modified: 09 Jun 2017 13:24
URI: http://irep.ntu.ac.uk/id/eprint/10284

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