PXD015456-1

PXD015456 is an original dataset announced via ProteomeXchange.

Title	Stress signaling and cellular proliferation reverse the effects of mitochondrial mistranslation
Description	The fidelity of translation is crucial in prokaryotes and for the nuclear-encoded proteins of eukaryotes, however little is known about the role of mistranslation in mitochondria and its effects on metabolism. We generated yeast and mouse models with error-prone and hyperaccurate mitochondrial translation fidelity and found that translation rate is more important than translational accuracy for cell function in mammals. We found that mitochondrial mistranslation reduces overall mitochondrial translation and the rate of respiratory complex assembly, however in mammals this is compensated for by increased mitochondrial protein stability and upregulation of the citric acid cycle. Moreover, mitochondrial stress signaling enables the recovery of mitochondrial translation via mitochondrial biogenesis, telomerase expression and cell proliferation, normalizing metabolism. Conversely, we show that increased fidelity of mitochondrial translation reduces the rate of protein synthesis without eliciting the mitochondrial stress response. Consequently, the rate of translation cannot be recovered causing dilated cardiomyopathy. Our findings reveal mammalian specific signaling pathways that can respond to changes in the fidelity of mitochondrial protein synthesis
HostingRepository	PRIDE
AnnounceDate	2019-11-08
AnnouncementXML	Submission_2019-11-08_08:49:36.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	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2019-09-16 01:12:13	ID requested
⏵ 1	2019-11-08 08:49:37	announced

Dataset with its publication pending

submitter keyword: metabolism, mitochondria, protein synthesis, stress response Abbreviations used: mitoribosome, mitochondrial ribosome

MRPS12, mitochondrial ribosomal protein of the small subunit 12

OXPHOS, oxidative phosphorylation

Oliver Rackham
contact affiliation	-Harry Perkins Institute of Medical Research, Nedlands, Western Australia 6009, Australia -School of Pharmacy and Biomedical Sciences, Curtin University, Bentley, Western Australia 6102, Australia -Curtin Health Innovation Research Institute, Curtin University, Bentley, WA 6102, Australia
contact email	oliver.rackham@curtin.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/2019/11/PXD015456

PRIDE project URI

• PRIDE
  1. PXD015456
     1. Label: PRIDE project
     2. Name: Stress signaling and cellular proliferation reverse the effects of mitochondrial mistranslation