PXD011741

PXD011741 is an original dataset announced via ProteomeXchange.

Title	Mouse HiRIEF LCMS Proteomics - Sedentary VS Exercise, WT VS PolgA mutant
Description	Mitochondrial dysfunction is implicated in aging and aging-related disorders, such as neurodegenerative diseases and stroke. To study the effects of progressive mitochondrial dysfunction, a homozygous knock-in mouse expressing a proof-reading deficient version of the nucleus-encoded catalytic subunit of mitochondrial DNA (mtDNA) polymerase (PolgA) has been developed. In the mtDNA mutator mouse the proofreading activity of PolgA has been abolished by a single amino acid change. PolgA is the catalytic subunit of the polymerase gamma, which is involved in replicating and proofreading the mitochondrial DNA. As a result, mtDNA mutator mice develop high levels of point mutations and linear deletions, which lead to several human-like phenotypes associated with aging, including reduced lifespan (42-44 weeks), weight loss, alopecia, anemia, kyphosis, osteoporosis, sarcopenia, loss of subcutaneous fat, and reduced fertility. We investigate the molecular mechanism through which exercise may improve the phenotype of the mtDNA mutator mouse, which is a model of premature aging induced by mitochondrial dysfunction. Remarkably, forced endurance exercise has been shown to rescue the progeroid aging phenotypes of the mtDNA mutator mice, and to induce systemic mitochondrial rejuvenation. Here, using voluntary, rather than forced exercise, we investigate the molecular mechanisms underlying such a dramatic improvement, and also assess the effect of exercise on brain tissues, such as cortex and striatum in our model. The complete proteome of key tissues (muscle, brain cortex, brain striatum) from exercising and sedentary mtDNA mutator mice as well as exercising and sedentary wild type mice is quantified using peptide high-resolution isoelectric focusing (HiRIEF) coupled with liquid chromatography tandem mass spectrometry (LC-MS/MS) with an isobaric tag (TMT10plex) strategy.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:50:15.807.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rui Branca
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-11-19 08:24:40	ID requested
1	2019-08-05 04:19:04	announced
⏵ 2	2024-10-22 04:50:18	announced	2024-10-22: Updated project metadata.

Ross JM, Coppotelli G, Branca RM, Kim KM, Lehti, ö J, Sinclair DA, Olson L, Voluntary exercise normalizes the proteomic landscape in muscle and brain and improves the phenotype of progeroid mice. Aging Cell, 18(6):e13029(2019) [pubmed]

10.1111/acel.13029;

curator keyword: Biological

submitter keyword: Exercise, PolgA, Muscle, Striatum,Mouse, Brain, LCMS, HiRIEF, Cortex, wt, Sedentary

Janne Lehtiö
contact affiliation	Dept. Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet, Sweden
contact email	janne.lehtio@ki.se
lab head
Rui Branca
contact affiliation	Clinical Proteomics Unit, Dep. of Oncology-Pathology
contact email	rui.mamede-branca@ki.se
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/2019/08/PXD011741

PRIDE project URI

• PRIDE
  1. PXD011741
     1. Label: PRIDE project
     2. Name: Mouse HiRIEF LCMS Proteomics - Sedentary VS Exercise, WT VS PolgA mutant