PXD000838

PXD000838 is an original dataset announced via ProteomeXchange.

Title	Mitochondrial proteomics investigation of a cellular model of impaired dopamine homeostasis, an early step in Parkinson's disease pathogenesis
Description	Impaired dopamine homeostasis is an early event in the pathogenesis of Parkinson's disease. Generation of intracellular reactive oxygen species consequent to dopamine oxidation leads to mitochondrial dysfunction and eventually cell death. Alterations in the mitochondrial proteome due to dopamine exposure were investigated in the SH-SY5Y human neuroblastoma cell line. The combination of two orthogonal proteomic approaches, two-dimensional electrophoresis and shotgun proteomics, was used to highlight the specific pathways perturbed by the increase of intracellular dopamine, in comparison with those perturbed by a specific mitochondrial toxin (4-methyphenylpyridinium, MPP+), a neurotoxin causing Parkinsonism-like symptoms in animal models. Proteins altered by MPP+ did not completely overlap with those affected by dopamine treatment. In particular, the MPP+ target complex I component NADH dehydrogenase [ubiquinone] iron-sulfur protein 3 was not affected by dopamine together with 26 other proteins. The comparison of proteomics approaches highlighted the fragmentation of some mitochondrial proteins, suggesting an alteration of the mitochondrial protease activity. Pathway and disease association analysis of the proteins affected by dopamine revealed the overrepresentation of the Parkinson's disease and the parkin-ubiquitin proteasomal system pathways and of gene ontologies associated to generation of precursor metabolites and energy, response to topologically incorrect proteins and programmed cell death. These alterations may be globally interpreted in part as the result of a direct effect of dopamine on mitochondria (e.g. alteration of the mitochondrial protease activity) and in part as the effect on mitochondria of a general activation of cellular processes (e.g. regulation of programmed cell death).
HostingRepository	PRIDE
AnnounceDate	2014-07-24
AnnouncementXML	Submission_2014-07-24_03:56:42.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Luisa Pieroni
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2014-03-17 08:34:36	ID requested
1	2014-04-15 07:15:47	announced
⏵ 2	2014-07-24 03:56:42	announced	Updated project metadata.

Alberio T, Bondi H, Colombo F, Alloggio I, Pieroni L, Urbani A, Fasano M, Mitochondrial proteomics investigation of a cellular model of impaired dopamine homeostasis, an early step in Parkinson's disease pathogenesis. Mol Biosyst, 10(6):1332-44(2014) [pubmed]

ProteomeXchange project tag: Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

curator keyword: Biomedical

submitter keyword: Dopamine

Human Proteome Project

Mitochondria

MPP+

Parkinson's disease

Respiratory chain

Shotgun proteomics

MSe

Andrea Urbani
contact affiliation	Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome, and Santa Lucia IRCCS Foundation, Rome, Italy
contact email	andrea.urbani@uniroma2.it
lab head
Luisa Pieroni
contact affiliation	Proteomics and Metabonomics Laboratory, CERC- S.Lucia Foundation Rome , AND Italy and Dep. of Surgery and Experimental Medicine, Faculty of Surgery and Medicine, University of Rome "Tor Vergata" Rome, Italy
contact email	luisa.pieroni@uniroma2.it
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2014/04/PXD000838

PRIDE project URI

• PRIDE
  1. PXD000838
     1. Label: PRIDE project
     2. Name: Mitochondrial proteomics investigation of a cellular model of impaired dopamine homeostasis, an early step in Parkinson's disease pathogenesis