PXD044615

PXD044615 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	2024-02-16
AnnouncementXML	Submission_2024-02-16_07:54:05.751.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD044615
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Friedel Drepper
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-18 05:04:42	ID requested
⏵ 1	2024-02-16 07:54:06	announced

10.6019/PXD044615;

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

Friedel Drepper
contact affiliation	Institute of Biology, University of Freiburg
contact email	f.drepper@biologie.uni-freiburg.de
lab head
Friedel Drepper
contact affiliation	University of Freiburg
contact email	f.drepper@biologie.uni-freiburg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044615
     1. Label: PRIDE project
     2. Name: A stop-and-go mechanism controls mitochondrial respiration