PXD045910-2

PXD045910 is an original dataset announced via ProteomeXchange.

Title	Physiological variability in mitochondrial rRNA may predispose to metabolic syndrome
Description	Objectives: Metabolic syndrome and its associated comorbidities are a growing concern in developed societies. Due to its polygenic nature, the genetic component of metabolic syndrome is only slowly being elucidated. Common mitochondrial DNA sequence variants have been associated with late-onset human diseases, including cardiovascular disease or type 2 diabetes mellitus, and may therefore be relevant players in the genetics of metabolic syndrome. Methods: In the present study, we investigate the effect of mitochondrial sequence variation on the metabolic phenotype in conplastic rat strains with identical nuclear but unique mitochondrial genomes that differ in the sequence of oxidative phosphorylation structural proteins, tRNAs and rRNAs. Results: Exposure to the high-fat diet led to the development of insulin resistance in the conplastic animals, which was associated with the reduced oxidative capacity of the heart (but not the liver) mitochondria. Reduced fatty acid oxidation led to the accumulation of bioactive diacylglycerols and subsequent inhibition of insulin signaling. Conclusions: We propose that these metabolic perturbations stem from the 12S rRNA sequence variation, which affects mitoribosome assembly and thus mitochondrial translation. Our work has demonstrated that physiological sequence variation in mitochondrial rRNA may be a relevant underlying factor in the progression of metabolic syndrome.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:54:47.386.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marek Vrbacky
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	methylthiolated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-05 05:13:45	ID requested
1	2024-08-13 04:20:07	announced
⏵ 2	2024-10-22 06:54:47	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: metabolic syndrome

mitochondrial haplotype

diacylglycerols

insulin signaling

Tomas Mracek
contact affiliation	Institute of Physiology of the Czech Academy of Sciences, Laboratory of Bioenergetics
contact email	tomas.mracek@fgu.cas.cz
lab head
Marek Vrbacky
contact affiliation	Czech Academy of Sciences
contact email	proteom.krc@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045910
     1. Label: PRIDE project
     2. Name: Physiological variability in mitochondrial rRNA may predispose to metabolic syndrome