PXD013659

PXD013659 is an original dataset announced via ProteomeXchange.

Title	Mrj1HA AP-MS in Cryptococcus neoformans
Description	The opportunistic fungal pathogen Cryptococcus neoformans must adapt to the mammalian environment to establish an infection. Proteins facilitating adaptation to novel environments, such as chaperones, may be required for virulence. In this study, we identified a novel mitochondrial co-chaperone, Mrj1, necessary for virulence in C. neoformans. The mrj1∆ and J-domain inactivated mutants had general growth defects, and were deficient in two major virulence factors, thermotolerance and capsule elaboration. The latter phenotype was associated with cell wall changes and increased capsular polysaccharide shedding. Accordingly, the mrj1∆ mutant was avirulent in a murine model of cryptococcosis. Mrj1 has a mitochondrial localization and co-immunoprecipitated with Qcr2, a core component of complex III of the ETC (Electron Transport Chain). The mrj1 mutants were deficient in mitochondrial functions including growth on alternative carbon sources, growth without iron, and mitochondrial polarization. They were also insensitive to complex III inhibitors and hypersensitive to an alternative oxidase (AOX) inhibitor suggesting that Mrj1 functions in respiration. In support of this conclusion, mrj1 mutants also had elevated basal oxygen consumption rates which were completely abolished by the addition of the AOX inhibitor, confirming that Mrj1 is required for mitochondrial respiration through complexes III and IV. Furthermore, inhibition of complex III phenocopied the capsule and cell wall defects of the mrj1 mutants. Taken together, these results indicate that Mrj1 is required for normal mitochondrial respiration, a key aspect of adaptation to the host environment and virulence.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:07:13.098.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Linda Horianopoulos
SpeciesList	scientific name: Cryptococcus neoformans var. grubii H99S; NCBI TaxID: 1432137;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-04-29 02:15:02	ID requested
1	2020-06-11 23:59:36	announced
⏵ 2	2024-10-22 05:07:20	announced	2024-10-22: Updated project metadata.

10.1128/mbio.01127-20;

Horianopoulos LC, Hu G, Caza M, Schmitt K, Overby P, Johnson JD, Valerius O, Braus GH, Kronstad JW, The Novel J-Domain Protein Mrj1 Is Required for Mitochondrial Respiration and Virulence in Cryptococcus neoformans. mBio, 11(3):(2020) [pubmed]

submitter keyword: Cryptococcus neoformans

James W. Kronstad
contact affiliation	Michael Smith Laboratories, University of British Columbia, Canada
contact email	kronstad@msl.ubc.ca
lab head
Linda Horianopoulos
contact affiliation	University of British Columbia
contact email	horianol@msl.ubc.ca
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/2020/06/PXD013659

PRIDE project URI

• PRIDE
  1. PXD013659
     1. Label: PRIDE project
     2. Name: Mrj1HA AP-MS in Cryptococcus neoformans