PXD044749-2

PXD044749 is an original dataset announced via ProteomeXchange.

Title	A stop-and-go mechanism controls mitochondrial respiration
Description	Oxidative phosphorylation (OXPHOS) is essential for the synthesis of the vast majority of ATP in eukaryotic cells. It is carried out by multi-protein assemblies that form the electron transport chain (ETC), which are coupled to the mitochondrial ATP synthase, which uses the proton gradient generated by the ETC to drive ATP synthesis. The assembly of the OXPHOS protein machinery requires the coordinated integration of proteins encoded in the nuclear and the mitochondrial genomes, imposing an additional layer of complexity. While the biogenesis of the individual OXPHOS complexes is well understood, it remains unknown how the assembly of the ETC and ATP synthase is coordinated to achieve the correct stoichiometry of the OXPHOS machinery. Here, we identify the mitochondrial regulatory hub for respiratory assembly (MiRA), which serves as a platform on which complex IV and complex V biogenesis are synchronised to ensure balanced assembly of the ETC and complex V. At the molecular level, this is achieved by a stop-and-go safeguarding mechanism: The novel mitochondrial protein Mra1 binds to and slows down complex IV assembly. Two Go signals are then required for assembly to proceed: Binding of the complex IV assembly factor Rcf2 and interaction with the mitoribosome, which translates the complex V subunit Atp9. Both Go signals induce the clipping and subsequent degradation of Mra1, relieving the molecular brake and allowing parallel maturation of complexes IV and V. The absence of the stop-and-go safety mechanism results in the formation of immature complexes, decreased ATP levels and reduced cell viability. The antagonistic activities at MiRA provide a regulated orchestration of complex IV and V assembly which is essential to avoid the predominance of either complex and an unbalanced ratio of OXPHOS complexes, thus ensuring the correct stoichiometry of protein machineries encoded by two different genomes.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:30:55.571.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marcin Luzarowski
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-22 13:01:07	ID requested
1	2024-02-16 11:21:39	announced
⏵ 2	2024-10-22 06:30:55	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: protein complex assembly,Mitochondria, complex stoichiometry, mitoribosome, respiratory chain

Nora Voegtle
contact affiliation	Center for Molecular Biology of Heidelberg University (ZMBH), 69120 Heidelberg, Germany
contact email	n.voegtle@zmbh.uni-heidelberg.de
lab head
Marcin Luzarowski
contact affiliation	University of Heidelberg
contact email	m.luzarowski@zmbh.uni-heidelberg.de
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/2024/02/PXD044749

PRIDE project URI

• PRIDE
  1. PXD044749
     1. Label: PRIDE project
     2. Name: A stop-and-go mechanism controls mitochondrial respiration