PXD054598

PXD054598 is an original dataset announced via ProteomeXchange.

Title	Tissue-specific responses to TFAM and mtDNA copy number manipulation in prematurely ageing mice
Description	Somatic mtDNA mutations are heavily implicated as important drivers of ageing and age-related diseases. Their pathological effect can be partially counteracted by increasing the absolute amount of wild-type mtDNA via moderately upregulating TFAM, a protein important for mtDNA packaging and expression. However, strong TFAM overexpression can also have detrimental effects as it results in hypercompaction of the mtDNA and subsequent impairment of mtDNA gene expression. In this study, we have experimentally addressed the propensity of moderate TFAM modulation to improve the premature ageing phenotypes of mtDNA mutator mice, carrying random mtDNA mutations. Surprisingly, we detect tissue-specific endogenous compensatory mechanisms acting in mtDNA mutator mice which largely affects the outcome of TFAM modulation. Accordingly, moderate overexpression of TFAM can have both negative and beneficial effects in different tissues of mtDNA mutator mice. We see a similar behavior for moderate TFAM reduction, which improves brown adipocyte tissue homeostasis, while other tissues are largely unaffected. Our findings highlight that regulation of copy number and gene expression of mtDNA is complex and cause tissue-specific effects that should be considered when modulating TFAM levels. Additionally, we suggest that TFAM is not the sole determinant of mtDNA copy number in situations where OXPHOS is compromised but other important players must be involved.
HostingRepository	PRIDE
AnnounceDate	2025-02-17
AnnouncementXML	Submission_2025-02-17_06:30:38.195.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Akos Vegvari
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-05 06:30:50	ID requested
⏵ 1	2025-02-17 06:30:38	announced

10.7554/ELIFE.104461.1;

submitter keyword: TFAM

Akos Vegvari
contact affiliation	Karolinska Institutet, Stockholm, Sweden
contact email	akos.vegvari@ki.se
lab head
Akos Vegvari
contact affiliation	Karolinska Institutet
contact email	akos.vegvari@ki.se
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD054598
     1. Label: PRIDE project
     2. Name: Tissue-specific responses to TFAM and mtDNA copy number manipulation in prematurely ageing mice