The Novel J-Domain Protein Mrj1 Is Required for Mitochondrial Respiration and Virulence in Cryptococcus neoformans.

MBio
Linda C HorianopoulosJames W Kronstad

Abstract

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 (mitochondrial respiration J-domain protein 1), necessary for virulence in C. neoformans The mrj1Δ and J-domain-inactivated mutants had general growth defects at both routine laboratory and human body temperatures and were deficient in the major virulence factor of capsule elaboration. The latter phenotype was associated with cell wall changes and increased capsular polysaccharide shedding. Accordingly, the mrj1Δ 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 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 supp...Continue Reading

References

Nov 15, 1975·FEBS Letters·P Mitchell
Jan 1, 1994·Critical Reviews in Biochemistry and Molecular Biology·U Brandt, B Trumpower
Jan 5, 2000·Clinical and Diagnostic Laboratory Immunology·J HuaJ K Lodge
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Sep 23, 2003·Infection and Immunity·Shamima AkhterJohn R Perfect
Nov 19, 2003·Molecular Microbiology·Amy J Reese, Tamara L Doering
Feb 22, 2005·Molecular Microbiology·Tianshun LianJames W Kronstad
Apr 2, 2005·Nature Reviews. Molecular Cell Biology·Tracey A Rouault, Wing-Hang Tong
Jul 1, 2005·Protein Science : a Publication of the Protein Society·Fritha HennessyGregory L Blatch
Jan 28, 2006·FEMS Microbiology Reviews·James P BurnieRuth C Matthews
May 16, 2006·FEMS Yeast Research·John R Perfect
Oct 24, 2006·Trends in Pharmacological Sciences·Vera Adam-Vizi, Christos Chinopoulos
Mar 21, 2007·PLoS Pathogens·Guanggan HuJames W Kronstad
May 23, 2007·Nucleic Acids Research·Paul HortonKenta Nakai
Dec 25, 2007·Eukaryotic Cell·Aki Yoneda, Tamara L Doering
Feb 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Leah E CowenSusan Lindquist
Aug 5, 2009·Proceedings of the National Academy of Sciences of the United States of America·Hansong MaRobin C May
Aug 26, 2009·Journal of Visualized Experiments : JoVE·Christopher GreggVladimir I Titorenko
Feb 23, 2010·PLoS Pathogens·Teresa R O'MearaJ Andrew Alspaugh
Jan 1, 2004·Biochemistry and Molecular Biology Education : a Bimonthly Publication of the International Union of Biochemistry and Molecular Biology·Santiago Garcia-Vallve
Jul 22, 2011·Nature·F Ulrich HartlManajit Hayer-Hartl
Oct 6, 2011·Journal of Proteome Research·Juliana CrestaniMarilene Henning Vainstein
Nov 9, 2011·Nucleic Acids Research·Jason E StajichDavid S Roos
Aug 30, 2012·Nature Methods·Caroline A SchneiderKevin W Eliceiri
Apr 17, 2013·Current Opinion in Microbiology·Leah E Cowen
Jun 12, 2013·Annual Review of Biochemistry·Yujin E KimF Ulrich Hartl
Dec 11, 2013·Molecular and Cellular Biology·Teresa R O'MearaJ Andrew Alspaugh
Oct 11, 2012·ACS Medicinal Chemistry Letters·Sheo B SinghJanet C Onishi
Jun 7, 2014·Current Opinion in Microbiology·Laurent Chatre, Miria Ricchetti

❮ Previous
Next ❯

Datasets Mentioned

BETA
PXD013659

Methods Mentioned

BETA
protein folding
reverse transcription-PCR
PCR
flow
fluorescence microscopy
flow cytometry
affinity purification
co-immunoprecipitation
protein assay
electrophoresis

Software Mentioned

GraphPad
BLASTp
GraphPad Prism6
MaxQuant
MitoFates
Zen
ImageJ
WoLF PSORT
GraphPad Prism
FlowJo

Related Concepts

Related Feeds

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Allergy and Asthma

Allergy and asthma are inflammatory disorders that are triggered by the activation of an allergen-specific regulatory t cell. These t cells become activated when allergens are recognized by allergen-presenting cells. Here is the latest research on allergy and asthma.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.