PXD025289

PXD025289 is an original dataset announced via ProteomeXchange.

Title	Mitochondrial Proteostasis Requires Genes Encoded in a Neurodevelopmental Syndrome Locus
Description	Eukaryotic cells maintain proteostasis through mechanisms that require cytoplasmic and mitochondrial translation. Genetic defects affecting cytoplasmic translation perturb synapse development, neurotransmission, and are causative of neurodevelopmental disorders such as Fragile X syndrome. In contrast, there is little indication that mitochondrial proteostasis, either in the form of mitochondrial protein translation and/or degradation, is required for synapse development and function. Here we focus on two genes deleted in a recurrent copy number variation causing neurodevelopmental disorders, the 22q11.2 microdeletion syndrome. We demonstrate that SLC25A1 and MRPL40, two genes present in the microdeleted segment and whose products localize to mitochondria, interact and are necessary for mitochondrial ribosomal integrity and proteostasis. Our Drosophila studies show that mitochondrial ribosome function is necessary for synapse neurodevelopment, function, and behavior. We propose that mitochondrial proteostasis perturbations, either by genetic or environmental factors, are a pathogenic mechanism for neurodevelopmental disorders.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-17_00:31:58.208.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Duc Duong
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-09 01:31:48	ID requested
⏵ 1	2022-02-17 00:31:59	announced

Gokhale A, Lee CE, Zlatic SA, Freeman AAH, Shearing N, Hartwig C, Ogunbona O, Bassell JL, Wynne ME, Werner E, Xu C, Wen Z, Duong D, Seyfried NT, Bearden CE, Ol, á, h VJ, Rowan MJM, Glausier JR, Lewis DA, Faundez V, Mitochondrial Proteostasis Requires Genes Encoded in a Neurodevelopmental Syndrome Locus. J Neurosci, 41(31):6596-6616(2021) [pubmed]

submitter keyword: LC-MSMS, FAIMS, Orbitrap

Victor Fuandez
contact affiliation	Victor Faundez MD, PhD Professor Dept. Cell Biology 615 Michael Street Whitehead 446 Atlanta, GA, 30322 Emory University
contact email	vfaunde@emory.edu
lab head
Duc Duong
contact affiliation	Center of Neurodegenerative Diseases
contact email	dduong@emory.edu
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/2022/02/PXD025289

PRIDE project URI

• PRIDE
  1. PXD025289
     1. Label: PRIDE project
     2. Name: Mitochondrial Proteostasis Requires Genes Encoded in a Neurodevelopmental Syndrome Locus