PXD061184

PXD061184 is an original dataset announced via ProteomeXchange.

Title	A bipartite motif of Mrx6 binds the Lon protease Pim1 N-terminal domain to confer substrates specificity and regulate mtDNA copy number
Description	Mitochondrial DNA (mtDNA) copy number regulation remains in- completely understood, despite its critical importance in cellular function. In Saccharomyces cerevisiae, the protein Mrx6 is part of the Pet20-domain-containing protein family, which includes three members: Mrx6, Pet20, and Sue1. Notably, absence of the MRX6 gene leads to increased mtDNA copy number. Here, we identify the C-terminus of Mrx6 as essential for its stability and interaction with the mitochondrial matrix protein Mam33. Deletion of Mam33 mimics the effect of Mrx6 loss, resulting in elevated mtDNA copy number. Bioinformatics, mutational analyses, and immunoprecipi- tation studies reveal that a subcomplex consisting of Mam33 and Mrx6 trimers can interact with the N-terminal substrate recognition domain of the conserved mitochondrial Lon protease Pim1 through a bipartite motif in the N-terminal Pet20-domain of Mrx6. Loss of Mrx6, its paralog Pet20, or its binding partner Mam33, as well as mutations disrupting the interaction between Mrx6 and Pim1, sta- bilize key mitochondrial proteins essential for mtDNA maintenance, the RNA polymerase Rpo41 and the HMG-box-containing protein Cim1. Our findings suggest that Mrx6, together with Pet20 and Mam33, regulates mtDNA copy number by modulating substrate degradation through the Lon protease. Notably, the absence of Mrx6 additionally alters Cim1’s function, preventing the detrimental effect on mtDNA maintenance observed upon Cim1 overexpres- sion. Given the presence of three Pet20-domain containing proteins in yeast, our findings on substrate recognition by the Lon protease has implications beyond mtDNA CN regulation.
HostingRepository	PRIDE
AnnounceDate	2025-11-18
AnnouncementXML	Submission_2025-11-18_05:19:36.686.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Serena Schwenkert
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: NEWT:4932;
ModificationList	No PTMs are included in the dataset
Instrument	impact II

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-25 08:38:05	ID requested
⏵ 1	2025-11-18 05:19:37	announced

Dataset with its publication pending

submitter keyword: Yeast, mitochondria, immunoprecipitation

Serena Schwenkert
contact affiliation	MSBioLMU Großhaderner Str. 2-4 82152 Planegg-Martinsried
contact email	serena.schwenkert@lmu.de
lab head
Serena Schwenkert
contact affiliation	LMU Munich
contact email	serena.schwenkert@lmu.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD061184
     1. Label: PRIDE project
     2. Name: A bipartite motif of Mrx6 binds the Lon protease Pim1 N-terminal domain to confer substrates specificity and regulate mtDNA copy number