PXD081636-1

PXD081636 is an original dataset announced via ProteomeXchange.

Title	Retrograde signalling mediates cellular adaptation to mitochondrial DNA copy number alterations
Description	Eukaryotic cells maintain multiple copies of the mitochondrial genome, which is essential for cellular metabolism. Accordingly, alterations in the mitochondrial DNA (mtDNA) copy number are associated with severe human diseases and ageing. However, the mechanisms through which cells regulate mtDNA copy number and the cellular consequences of altered copy number remain poorly understood. Here, using budding yeast as a model, we show that mtDNA copy number is determined by the amount of three limiting factors, Mip1, Abf2, and Rim1. By synthetically tuning the concentrations of only these three proteins, we can modulate mtDNA dosage inside the cell. This revealed that cells are surprisingly robust to mtDNA copy number alterations, with increased copy numbers even accelerating cell growth. Our findings suggest that this robustness is due to protein dosage compensation and independent regulation of mitochondrial morphology. Mechanistically, we identified a critical role of the retrograde signalling pathway for this adaptation. We show that signalling from mitochondria to the nucleus is upregulated in cells with higher mtDNA copy number, and disruption of this regulation diminishes their faster growth. Taken together, our work reveals regulatory principles that allow cells to adapt to mtDNA copy number alterations.
HostingRepository	PRIDE
AnnounceDate	2026-07-26
AnnouncementXML	Submission_2026-07-25_21:21:23.966.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michael Lanz
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: NEWT:4932;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2026-07-24 18:01:18	ID requested
⏵ 1	2026-07-25 21:21:24	announced

Dataset with its publication pending

submitter keyword: Mitochondria, yeast, retrograde signalling, cell size

Kurt Schmoller
contact affiliation	Institute of Functional Epigenetics, Molecular Targets and Therapeutics Center, Helmholtz Zentrum München, Neuherberg, Germany
contact email	kurt.schmoller@helmholtz-munich.de
lab head
Michael Lanz
contact affiliation	Stanford University
contact email	mikelanz@stanford.edu
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/2026/07/PXD081636

PRIDE project URI

• PRIDE
  1. PXD081636
     1. Label: PRIDE project
     2. Name: Retrograde signalling mediates cellular adaptation to mitochondrial DNA copy number alterations