PXD002760

PXD002760 is an original dataset announced via ProteomeXchange.

Title	Muscle biopsies from human neuromuscular diseases with dystrophic, inflammatory and myopathic pathology reveal common alterations in mitochondrial function
Description	Neuromuscular disorders (NMDs) are clinically and genetically heterogenous and manifest as dystrophic, inflammatory and myopathic pathologies, among others. Our previous study on the cardiotoxin (CTX) mouse model of myodegeneration and inflammation linked muscle pathology with mitochondrial damage and oxidative stress. In this study, we investigated whether human NMDs display mitochondrial changes. Muscle biopsies from NMD patients, represented by dystrophic pathology [dysferlinopathy (dysfy); n=43], inflammatory pathology [inflammatory myopathy (IM); n=24] and myopathic pathology [distal myopathy with rimmer vacuoles (DMRV); n=31] were analysed. Mitochondrial damage was revealed in all NMDs by Enzyme histochemistry (SDH and SDH-COX deficiency), electron microscopy (vacuolation and abnormal ultrastructures) and biochemical assays (significantly increased ADP/ATP ratio). Proteomic analysis of muscle mitochondria from all three NMDs by Isobaric tag for relative and absolute quantitation (iTRAQ) labelling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis demonstrated down-regulation of electron transport chain (ETC) complex subunits, assembly factors and Krebs cycle enzymes. Most of the differentially expressed proteins were common among the three pathologies. Assay of ETC and Krebs cycle enzyme activities validated the MS data. Mitochondrial proteins from muscle pathologies also displayed higher trp oxidation and the same was corroborated in the CTX model. Molecular modelling predicted trp oxidation to alter the local structure of mitochondrial proteins. Our data highlight mitochondrial alterations in muscle pathologies, represented by structural changes, altered mitochondrial proteome and protein oxidation status, thereby establishing the importance of mitochondrial damage in human NMDs.
HostingRepository	PRIDE
AnnounceDate	2016-04-04
AnnouncementXML	Submission_2016-04-04_06:27:06.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Srinivas Bharath
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iTRAQ4plex-116 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2015-08-18 08:55:29	ID requested
⏵ 1	2016-04-04 06:27:08	announced

Sunitha B, Gayathri N, Kumar M, Keshava Prasad TS, Nalini A, Padmanabhan B, Srinivas Bharath MM, Muscle biopsies from human muscle diseases with myopathic pathology reveal common alterations in mitochondrial function. J Neurochem, 138(1):174-91(2016) [pubmed]

curator keyword: Biomedical

submitter keyword: dystrophy, proteomics, Orbitrap

M. M. Srinivas Bharath
contact affiliation	Department of Neurochemistry, NIMHANS, No. 2900, Hosur Road, Bangalore-560029, Karnataka, India
contact email	bharath@nimhans.kar.nic.in
lab head
Srinivas Bharath
contact affiliation	Department of Neurochemistry National Institute of Mental Health and Neurosciences (NIMHANS)
contact email	thathachar@rediffmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002760
     1. Label: PRIDE project
     2. Name: Muscle biopsies from human neuromuscular diseases with dystrophic, inflammatory and myopathic pathology reveal common alterations in mitochondrial function