PXD024633

PXD024633 is an original dataset announced via ProteomeXchange.

Title	Mitochondrial mistranslation modulated by metabolic stress causes cardiovascular disease and reduced life-span
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 and their effects on lifespan. Intriguingly, although both mutations are metabolically beneficial in reducing body weight, decreasing circulating insulin and increasing glucose tolerance during a high-fat diet, they manifest divergent (either deleterious or beneficial) outcomes in a tissue-specific manner. In two distinct organ types that are commonly affected by metabolic disease, the heart and the liver, Mrps12ep/ep mice were protected against heart defects but sensitive towards lipid accumulation in the liver, activating genes involved in steroid and amino acid metabolism. In contrast, enhanced translational accuracy in Mrps12ha/ha mice protected the liver from a high-fat diet through activation of liver proliferation programs, but enhanced the development of severe hypertrophic cardiomyopathy and led to reduced lifespan. While these findings reflect the complex transcriptional and cell signalling responses that differ between post-mitotic (heart) and highly proliferative (liver) tissues, they also suggest that trade-offs between the rate and fidelity of mitochondrial protein synthesis dictate tissue-specific outcomes toward commonly encountered stressful environmental conditions or aging.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-16_16:46:50.363.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mark Larance
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-10 02:21:34	ID requested
⏵ 1	2022-02-16 16:46:51	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: Mouse, Heart, Mitochondria

Mark Larance
contact affiliation	Charles Perkins Centre, School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW, Australia.
contact email	mark.larance@sydney.edu.au
lab head
Mark Larance
contact affiliation	The University of Sydney
contact email	mark.larance@sydney.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024633
     1. Label: PRIDE project
     2. Name: Mitochondrial mistranslation modulated by metabolic stress causes cardiovascular disease and reduced life-span