PXD023902

PXD023902 is an original dataset announced via ProteomeXchange.

Title	Increased levels of the mitochondrial import factor Mia40 can prevent the aggregation of polyQ proteins in the cytosol
Description	The formation of protein aggregates is a hallmark of neurodegenerative diseases. Observations on patient material and model systems demonstrated links between aggregate formation and declining mitochondrial functionality, but the causalities remained unclear. We used yeast as model system to analyze the relevance of mitochondrial processes for the behavior of an aggregation-prone polyQ protein derived from human huntingtin. Induction of Q97-GFP rapidly leads to insoluble cytosolic aggregates and cell death. Although these aggregates impaired mitochondrial respiration only slightly, they interfered with efficient import of mitochondrial precursor proteins. Mutants in the import component Mia40 were hypersensitive to Q97-GFP. Even more surprising, Mia40 overexpression strongly suppressed the formation of toxic Q97-GFP aggregates both in yeast and in human cells. Based on our observations, we propose that the posttranslational import into mitochondria competes with aggregation-prone cytosolic proteins for chaperones and proteasome capacity. Owing to its rate-limiting role for mitochondrial protein import, Mia40 acts as regulatory component in this competition with direct relevance for cytosolic proteostatic stability. Thus, targeting Mia40 might offer exciting therapeutic potential in the future. In this dataset we analyzed the soluble proteome of wild type and Mia40 overexpression yeast cells in response to the expression of polyQ proteins.
HostingRepository	PRIDE
AnnounceDate	2021-08-06
AnnouncementXML	Submission_2021-08-06_01:20:22.386.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Frank Stein
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-31 22:54:08	ID requested
1	2021-08-05 02:55:34	announced
⏵ 2	2021-08-06 01:20:23	announced	2021-08-06: Updated project metadata.

10.15252/EMBJ.2021107913;

Schlagowski AM, Kn, ö, ringer K, Morlot S, S, á, nchez Vicente A, Flohr T, Kr, ä, mer L, Boos F, Khalid N, Ahmed S, Schramm J, Murschall LM, Haberkant P, Stein F, Riemer J, Westermann B, Braun RJ, Winklhofer KF, Charvin G, Herrmann JM, Increased levels of mitochondrial import factor Mia40 prevent the aggregation of polyQ proteins in the cytosol. EMBO J, 40(16):e107913(2021) [pubmed]

submitter keyword: Huntingtin / Mia40 / Mitochondria / Protein aggregation / Protein translocation

Johannes M. Herrmann
contact affiliation	University of Kaiserslautern, Cell Biology, Germany
contact email	hannes.herrmann@biologie.uni-kl.de
lab head
Frank Stein
contact affiliation	EMBL
contact email	frank.stein@embl.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023902
     1. Label: PRIDE project
     2. Name: Increased levels of the mitochondrial import factor Mia40 can prevent the aggregation of polyQ proteins in the cytosol