PXD039850

PXD039850 is an original dataset announced via ProteomeXchange.

Title	The Orf9b protein of SARS-CoV-2 modulates mitochondrial protein biogenesis - Yeast Data Set
Description	Viruses often induce a complex rewiring of cellular physiology to maximize their propagation. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) expresses high amounts of the viral antagonistic protein Orf9b. Increased amounts and mutated versions of Orf9b were found to correlate with improved transmission of more evolved virus forms such as the Alpha and Omicron variants. Orf9b binds to the mitochondrial surface receptor Tom70 which stiffens its highly flexible structure. Tom70 plays a critical role in the antiviral response since it serves as recruiting factor for the mitochondrial antiviral signaling (MAVS) protein. However, the predominant and MAVS-independent role of Tom70 is that of a receptor component of the mitochondrial import system. Whether Orf9b also interferes with this predominant function of Tom70 is unknown. In this study, we expressed Orf9b in human HEK293 cells and observed the Orf9b-mediated depletion of mitochondrial proteins, particularly in respiring cells. The spectrum of depleted mitochondrial proteins was comparable to that of cells in which Tom70 was depleted, consistent with an Orf9b-mediated impairment of Tom70-dependent protein import. To exclude that the observed depletion was caused by the antiviral response triggered by Orf9b expression, we generated a yeast system in which the yeast Tom70 was replaced by a humanized version of Tom70. Upon expression of Orf9b in these cells, we again observed a general but moderate reduction of mitochondrial proteins. Similar to the situation in human cells, a number of mitochondrial proteins were particular sensitive to Orf9b expression, suggesting a rather specific modulation of the mitochondrial import system. In vitro import experiments with semi-intact cells confirmed this Orf9b-mediated impairment of the mitochondrial protein import. Thus, the SARS-CoV-2 virus seems to modulate the mitochondrial proteome by a direct effect of Orf9b on mitochondrial Tom70-dependent protein import.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:02:11.467.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Markus Räschle
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	2023-02-03 15:29:14	ID requested
1	2023-08-30 04:13:30	announced
2	2023-11-14 07:58:32	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 06:02:11	announced	2024-10-22: Updated project metadata.

10.1083/JCB.202303002;

submitter keyword: Orf9b, mitochondrial import

Markus Räschle
contact affiliation	Molecular Genetics, RPTU Kaiserslautern, Germany
contact email	raeschle@rhrk.uni-kl.de
lab head
Markus Räschle
contact affiliation	Technical University Kaiserslautern
contact email	raeschle@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/2023/08/PXD039850

PRIDE project URI

• PRIDE
  1. PXD039850
     1. Label: PRIDE project
     2. Name: The Orf9b protein of SARS-CoV-2 modulates mitochondrial protein biogenesis - Yeast Data Set