PXD011789

PXD011789 is an original dataset announced via ProteomeXchange.

Title	Mitoprotein-induced stress launches a global transcriptional fail-safe program
Description	Most mitochondrial proteins are synthesized as cytosolic precursor proteins before being imported into mitochondria. Cytosolic accumulation of mitochondrial precursors hazards cellular fitness and is associated with a growing number of diseases, but is not observed under physiological conditions. Individual mechanisms that allow cells to avoid cytosolic accumulation of mitochondrial precursors have recently been discovered, but their interplay and regulation remain elusive. Here we show that cells rapidly launch a global transcriptional program to restore cellular proteostasis after induction of a “clogger” protein that reduces the number of available mitochondrial import sites. Cells upregulate the protein folding and proteolytic systems in the cytosol and downregulate both the cytosolic translation machinery and many mitochondrial metabolic enzymes, presumably to relieve the workload of the overstrained mitochondrial import system. We show that this transcriptional remodeling is a combination of a “wideband” core response regulated by the transcription factors Hsf1 and Rpn4 and a unique mitoprotein-induced downregulation of the oxidative phosphorylation components, the most abundant group of precursorsmediated by an inactivation of the Hap2/3/4/5 complex. These findings depict the first comprehensive, time-resolved model of adaptations to mitochondrial import impairment. This reveals the regulation of previously described reactions and combines them with a so far unidentified mitochondrion-specific arm into an overarching coordinated network of the cellular mitoprotein-induced stress response.
HostingRepository	PRIDE
AnnounceDate	2019-01-14
AnnouncementXML	Submission_2019-04-12_00:32:40.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Felix Boos
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-11-21 23:54:59	ID requested
1	2019-01-13 23:42:27	announced
⏵ 2	2019-04-12 00:32:42	announced	Updated publication reference for PubMed record(s): 30886345.

Boos F, Kr, ä, mer L, Groh C, Jung F, Haberkant P, Stein F, Wollweber F, Gackstatter A, Z, ö, ller E, van der Laan M, Savitski MM, Benes V, Herrmann JM, Mitochondrial protein-induced stress triggers a global adaptive transcriptional programme. Nat Cell Biol, 21(4):442-451(2019) [pubmed]

curator keyword: Biological

submitter keyword: Mitochondria, Protein Import, Stress Response, Yeast, Proteasome, Chaperones, Oxidative Phosphorylation

Johannes M. Herrmann
contact affiliation	University of Kaiserlautern Cell Biology
contact email	hannes.herrmann@biologie.uni-kl.de
lab head
Felix Boos
contact affiliation	University of Kaiserslautern
contact email	fboos@rhrk.uni-kl.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/2019/01/PXD011789

PRIDE project URI

• PRIDE
  1. PXD011789
     1. Label: PRIDE project
     2. Name: Mitoprotein-induced stress launches a global transcriptional fail-safe program