PXD021880-1

PXD021880 is an original dataset announced via ProteomeXchange.

Title	TDP-43 aggregation induced by oxidative stress causes global mitochondrial imbalance in ALS
Description	When mutant superoxide dismutase 1 (SOD1) was first linked to amyotrophic lateral sclerosis (ALS), it was thought that ALS is a disease of oxidative stress. Since the discovery of multiple ALS-linked genes involved in RNA processing and proteostasis, most recent research has been focused on molecular defects induced by those mutant genes, but whether and how oxidative stress might contribute to magnification of those molecular defects have remained unaddressed. Strikingly, a hallmark of both familial and sporadic ALS is the aggregation of the essential DNA/RNA binding protein TDP-43, which is thought to cause simultaneous loss-of-nuclear function and gain-of-cytoplasmic toxicity. A central unanswered question is what triggers ALS in adult followed by rapid and irreversible progression? Here we report that neuronal cells are particularly prone to oxidative stress to trigger TDP-43 aggregation, which in turn sponges a large subset of microRNAs and proteins to cause both up-regulation and functional depletion of different sets of gene products. Remarkably, a large fraction of those functionally perturbed genes are nuclear genome-encoded mitochondrial proteins, thus resulting in a global mitochondrial imbalance, which further augments oxidative stress. We propose that this ferocious cycle driven by oxidative stress in combination with causal mutations in critical genes may underlie ALS onset and progression.
HostingRepository	PRIDE
AnnounceDate	2020-11-20
AnnouncementXML	Submission_2020-11-20_06:26:27.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	kai wu
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-07 07:55:35	ID requested
⏵ 1	2020-11-20 06:26:27	announced

Dataset with its publication pending

submitter keyword: mouse N2a H2O2 ALS let-7c

Yu Zhou
contact affiliation	State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan 430072, China
contact email	yu.zhou@whu.edu.cn
lab head
kai wu
contact affiliation	Wuhan university
contact email	kai.wu@whu.edu.cn
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/2020/11/PXD021880

PRIDE project URI

• PRIDE
  1. PXD021880
     1. Label: PRIDE project
     2. Name: TDP-43 aggregation induced by oxidative stress causes global mitochondrial imbalance in ALS