Ydj1 governs fungal morphogenesis and stress response, and facilitates mitochondrial protein import via Mas1 and Mas2

Xie, Jinglin Lucy; Bohovych, Iryna; Wong, Erin Oi-Yan; Lambert, Jean-Philippe; Gingras, Anne‐Claude; Khalimonchuk, Oleh; Cowen, Leah E.; Leach, Michelle

doi:10.15698/mic2017.10.594

Cited by 32 publications

(31 citation statements)

References 73 publications

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“…Chaperones in the Hsp40 family are referred to as J proteins due to the presence of a 70 amino acid J domain that contains the conserved histidine-proline-aspartate (HPD) tripeptide [27,84]. In S. cerevisiae, Ydj1, a member of the Hps40 family, regulates Hsp70 ATPase activity, influencing protein folding [84][85][86][87]. In addition, studies in S. cerevisiae have revealed several ER-resident J proteins, notably Sec63, Hlj1, Erj5, Scj1, and Jem1, but only Jem1p has been extensively investigated in C. albicans [27].…”

Section: Protein Folding and Maturationmentioning

confidence: 99%

The Role of Secretory Pathways in Candida albicans Pathogenesis

Rollenhagen

Mamtani

et al. 2020

JoF

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Candida albicans is a fungus that is a commensal organism and a member of the normal human microbiota. It has the ability to transition into an opportunistic invasive pathogen. Attributes that support pathogenesis include secretion of virulence-associated proteins, hyphal formation, and biofilm formation. These processes are supported by secretion, as defined in the broad context of membrane trafficking. In this review, we examine the role of secretory pathways in Candida virulence, with a focus on the model opportunistic fungal pathogen, Candida albicans.

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Section: Protein Folding and Maturationmentioning

confidence: 99%

The Role of Secretory Pathways in Candida albicans Pathogenesis

Rollenhagen

Mamtani

et al. 2020

JoF

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“…Moreover, the knockdown of OsDjA6 enhanced the resistance of Oryza sativa to Magnaporthe oryzae (Zhong et al, 2018). For Candida albicans, Ydj1 loss resulted in the failure of morphogenetic switch from yeast to filamentous form (Xie et al, 2017). However, the function of DnaJ protein in macro basidiomycete fungi is less well-known.…”

Section: Introductionmentioning

confidence: 99%

Hsp40 Protein LeDnaJ07 Enhances the Thermotolerance of Lentinula edodes and Regulates IAA Biosynthesis by Interacting LetrpE

et al. 2020

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Our previous study found that LeDnaJ07 RNAi decreased Lentinula edodes resistance to heat stress and Trichoderma atroviride infection. In this study, the structure and function of the LeDnaJ07 gene was analyzed by gene cloning and overexpression in L. edodes stress-sensitive strain YS55 via the Agrobacterium-mediated transformation method. Transformants were confirmed by qRT-PCR, fluorescence observation and Southern blotting. Overexpression of LeDnaJ07 in YS55 not only enhanced L. edodes mycelial resistance to heat stress but also facilitated mycelial growth. In the presence of heat stress, the intracellular IAA content showed a significant increase in the two LeDnaJ07 overexpression strains but only a slight change in the YS55 wild type strain. Moreover, the interaction between LeDnaJ07 and LetrpE was demonstrated via Y2H and BiFC assays. These results suggested that LeDnaJ07 may be involved in regulating IAA biosynthesis and the resistance of L. edodes to heat stresses via interacting with LetrpE.

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“…Later studies also showed that Hsp90 was required for thermotolerance and localized to the cell surface (14). Surprisingly, the J-domain proteins (JDPs; often referred to as Hsp40s) that act as co-chaperones and critically direct Hsp70 function have not been characterized in C. neoformans despite the large size of the family and their reported importance in other fungal pathogens (15)(16)(17)(18)(19).…”

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confidence: 99%

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

Horianopoulos

Caza

et al. 2020

mBio

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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 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. IMPORTANCE Cryptococcus neoformans is the causative agent of cryptococcal meningitis, a disease responsible for ∼15% of all HIV-related deaths. Unfortunately, development of antifungal drugs is challenging because potential targets are conserved between humans and C. neoformans. In this context, we characterized a unique J-domain protein, Mrj1, which lacks orthologs in humans. We showed that Mrj1 was required for normal mitochondrial respiration and that mutants lacking Mrj1 were deficient in growth, capsule elaboration, and virulence. Furthermore, we were able to phenocopy the defects in growth and capsule elaboration by inhibiting respiration. This result suggests that the role of Mrj1 in mitochondrial function was responsible for the observed virulence defects and reinforces the importance of mitochondria to fungal pathogenesis. Mitochondria are difficult to target, as their function is also key to human cells; however, Mrj1 presents an opportunity to target a unique fungal protein required for mitochondrial function and virulence in C. neoformans.

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Ydj1 governs fungal morphogenesis and stress response, and facilitates mitochondrial protein import via Mas1 and Mas2

Cited by 32 publications

References 73 publications

The Role of Secretory Pathways in Candida albicans Pathogenesis

The Role of Secretory Pathways in Candida albicans Pathogenesis

Hsp40 Protein LeDnaJ07 Enhances the Thermotolerance of Lentinula edodes and Regulates IAA Biosynthesis by Interacting LetrpE

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

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