PXD021762

PXD021762 is an original dataset announced via ProteomeXchange.

Title	Mitochondrial mistranslation is modulated by metabolic stress
Description	Changes in the rate and fidelity of mitochondrial protein synthesis impact the metabolic and physiological roles of mitochondria. Here we explored how environmental stress in the form of a high fat diet modulates mitochondrial translation using mutant mice with error-prone (Mrps12ep/ep) or hyper-accurate (Mrps12ha/ha) mitochondrial ribosomes. We find that while, metabolically both mutations are beneficial in reducing body weight, decreasing circulating insulin and increasing glucose tolerance they cause tissue specific defects when placed on a high fat diet. In contrast to the effect of the mutations on a normal diet the Mrps12ha/ha mice show more pronounced phenotypic and molecular defects as a result of the slow, accurate nature of their protein synthesis. While the Mrps12ep/ep mice accumulate more fat, exhibit larger vacuoles in the liver and lose glucose tolerance, the Mrps12ha/ha mice develop severe hypertrophic cardiomyopathy and hypoxia due to the stress of the diet, showing that benefit or detriment of error-prone and hyper-accurate protein synthesis in mitochondria is dependent on tissue and environmental conditions.
HostingRepository	PRIDE
AnnounceDate	2021-09-09
AnnouncementXML	Submission_2021-09-09_09:24:29.578.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Irina Kuznetsova
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-30 01:27:30	ID requested
⏵ 1	2021-09-09 09:24:30	announced

Richman TR, Ermer JA, Siira SJ, Kuznetsova I, Brosnan CA, Rossetti G, Baker J, Perks KL, Cserne Szappanos H, Viola HM, Gray N, Larance M, Hool LC, Zuryn S, Rackham O, Filipovska A, Mitochondrial mistranslation modulated by metabolic stress causes cardiovascular disease and reduced lifespan. Aging Cell, 20(7):e13408(2021) [pubmed]

submitter keyword: mitochondria, metabolism, protein synthesis

Aleksandra Filipovska
contact affiliation	Harry Perkins Institute of Medical Research and 2ARC Centre of Excellence in Synthetic Biology, QEII Medical Centre, Nedlands, Western Australia 6009, Australia
contact email	aleksandra.filipovska@uwa.edu.au
lab head
Irina Kuznetsova
contact affiliation	UWA
contact email	irina.kuznetsova@perkins.org.au
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/2021/09/PXD021762

PRIDE project URI

• PRIDE
  1. PXD021762
     1. Label: PRIDE project
     2. Name: Mitochondrial mistranslation is modulated by metabolic stress