PXD002125

PXD002125 is an original dataset announced via ProteomeXchange.

Title	Label free quantitative proteomics reveals survival mechanisms developed by Hypertrophic chondrocytes under ER stress
Description	Emerging evidence implicates ER stress caused by unfolded mutant proteins in chondrocytes as the underlying pathology of chondrodysplasias. ER stress is triggered in hypertrophic chondrocytes (HCs) in a mouse model (13del) of metaphyseal chondrodysplasia type Schmid (MCDS) caused by misfolded mutant collagen X proteins, but the HCs do not undergo apoptosis, rather chondrocyte differentiation is altered causing skeletal abnormality. How 13del HCs can escape from apoptosis and survive ER stress is not understood. We compared using label-free quantitative mass spectrometry approach the proteomes of HCs isolated from 13del growth plates with normal HCs. In this paper we reveal significant changes in levels of proteins involved in in actin remodeling, glycolysis and ER-mitochondria communication in 13del HCs chondrocytes. Previous in vitro studies of chronic ER stress showed down-regulation of glycolysis and disrupted mitochondrial function leading to cell death. Our data showed that glucose uptake was maintained in ATDC5 chondrocytic cell lines expressing 13del collagen X. Furthermore expression of mitochondrial calcium channels was reduced while mitochondrial membrane polarity was maintained in in vivo 13del chondrocytes. Thus we propose that 13del HCs survive by a mechanism whereby changes in ER-mitochondria communication reduce import of calcium coupled with maintenance of mitochondrial membrane polarity.
HostingRepository	PRIDE
AnnounceDate	2015-11-25
AnnouncementXML	Submission_2015-11-25_05:44:24.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	MATEUSZ KUDELKO
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2015-04-30 01:24:09	ID requested
⏵ 1	2015-11-25 05:44:25	announced

Kudelko M, Chan CW, Sharma R, Yao Q, Lau E, Chu IK, Cheah KS, Tanner JA, Chan D, Label-Free Quantitative Proteomics Reveals Survival Mechanisms Developed by Hypertrophic Chondrocytes under ER Stress. J Proteome Res, 15(1):86-99(2016) [pubmed]

curator keyword: Biomedical, Biological

submitter keyword: glycolysis, mitochondrial membrane polarity, calcium signaling, metaphyseal chondrodysplasia type schmid

Danny Chan
contact affiliation	Professor and Assistant Dean
contact email	chand@hku.hk
lab head
MATEUSZ KUDELKO
contact affiliation	HKU Biochemistry
contact email	mkudelko@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002125
     1. Label: PRIDE project
     2. Name: Label free quantitative proteomics reveals survival mechanisms developed by Hypertrophic chondrocytes under ER stress