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

Jinglin L Xie, Iryna Bohovych, Erin O Y Wong, Jean-Philippe Lambert, Anne-Claude Gingras, Oleh Khalimonchuk, Michelle Leach, Leah E. Cowen

Research output: Contribution to journalArticle

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Abstract

Mitochondria underpin metabolism, bioenergetics, signalling, development and cell death in eukaryotes. Most of the ~1,000 yeast mitochondrial proteins are encoded in the nucleus and synthesised as precursors in the cytosol, with mitochondrial import facilitated by molecular chaperones. Here, we focus on the Hsp40 chaperone Ydj1 in the fungal pathogen Candida albicans, finding that it is localised to both the cytosol and outer mitochondrial membrane, and is required for cellular stress responses and for filamentation, a key virulence trait. Mapping the Ydj1 protein interaction network highlighted connections with co-chaperones and regulators of filamentation. Furthermore, the mitochondrial processing peptidases Mas1 and Mas2 were highly enriched for interaction with Ydj1. Additional analysis demonstrated that loss of MAS1, MAS2 or YDJ1 perturbs mitochondrial morphology and function. Deletion of YDJ1 impairs import of Su9, a protein that is cleaved to a mature form by Mas1 and Mas2. Thus, we highlight a novel role for Ydj1 in cellular morphogenesis, stress responses, and mitochondrial import in the fungal kingdom.
Original languageEnglish
Pages (from-to)342-361
Number of pages20
JournalMicrobial Cell
Volume4
Issue number10
DOIs
Publication statusPublished - 2 Oct 2017

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Mitochondrial Proteins
Morphogenesis
Cytosol
Protein Interaction Maps
Molecular Chaperones
Fungal Proteins
Mitochondrial Membranes
Eukaryota
Candida albicans
Energy Metabolism
Virulence
Mitochondria
Cell Death
Proteins
mitochondrial processing peptidase

Keywords

  • candida albicans
  • stress
  • mitochondria
  • morphogenesis
  • heat shock
  • mitochondrial processing peptidases

Cite this

Xie, J. L., Bohovych, I., Wong, E. O. Y., Lambert, J-P., Gingras, A-C., Khalimonchuk, O., ... Cowen, L. E. (2017). Ydj1 governs fungal morphogenesis and stress response, and facilitates mitochondrial protein import via Mas1 and Mas2. Microbial Cell, 4(10), 342-361. https://doi.org/10.15698/mic2017.10.594

Ydj1 governs fungal morphogenesis and stress response, and facilitates mitochondrial protein import via Mas1 and Mas2. / Xie, Jinglin L; Bohovych, Iryna; Wong, Erin O Y; Lambert, Jean-Philippe ; Gingras, Anne-Claude; Khalimonchuk, Oleh; Leach, Michelle; Cowen, Leah E. .

In: Microbial Cell, Vol. 4, No. 10, 02.10.2017, p. 342-361.

Research output: Contribution to journalArticle

Xie, JL, Bohovych, I, Wong, EOY, Lambert, J-P, Gingras, A-C, Khalimonchuk, O, Leach, M & Cowen, LE 2017, 'Ydj1 governs fungal morphogenesis and stress response, and facilitates mitochondrial protein import via Mas1 and Mas2', Microbial Cell, vol. 4, no. 10, pp. 342-361. https://doi.org/10.15698/mic2017.10.594
Xie, Jinglin L ; Bohovych, Iryna ; Wong, Erin O Y ; Lambert, Jean-Philippe ; Gingras, Anne-Claude ; Khalimonchuk, Oleh ; Leach, Michelle ; Cowen, Leah E. . / Ydj1 governs fungal morphogenesis and stress response, and facilitates mitochondrial protein import via Mas1 and Mas2. In: Microbial Cell. 2017 ; Vol. 4, No. 10. pp. 342-361.
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abstract = "Mitochondria underpin metabolism, bioenergetics, signalling, development and cell death in eukaryotes. Most of the ~1,000 yeast mitochondrial proteins are encoded in the nucleus and synthesised as precursors in the cytosol, with mitochondrial import facilitated by molecular chaperones. Here, we focus on the Hsp40 chaperone Ydj1 in the fungal pathogen Candida albicans, finding that it is localised to both the cytosol and outer mitochondrial membrane, and is required for cellular stress responses and for filamentation, a key virulence trait. Mapping the Ydj1 protein interaction network highlighted connections with co-chaperones and regulators of filamentation. Furthermore, the mitochondrial processing peptidases Mas1 and Mas2 were highly enriched for interaction with Ydj1. Additional analysis demonstrated that loss of MAS1, MAS2 or YDJ1 perturbs mitochondrial morphology and function. Deletion of YDJ1 impairs import of Su9, a protein that is cleaved to a mature form by Mas1 and Mas2. Thus, we highlight a novel role for Ydj1 in cellular morphogenesis, stress responses, and mitochondrial import in the fungal kingdom.",
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note = "We thank Zhen-Yuan Lin for help in the preparation of the AP-MS samples, and Cathy Collins for technical assistance. MDL is supported by a Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust 096072), LEC is supported by a Canada Research Chair in Microbial Genomics and Infectious Disease and by Cana-dian Institutes of Health Research (CIHR) Grants MOP-119520 and MOP-86452. OK is supported by National Insti-tutes of Health grant 5R01GM108975. A-CG is supported by a CIHR Foundation Grant (FDN143301), Genome Cana-da Genomics Innovation Network (GIN) Node and Tech-nical Development Grants, and a Canada Research Chair in Functional Proteomics. J-PL was supported by a TD Bank Health Research Fellowship at the Lunenfeld-Tanenbaum Research Institute and by a Scholarship for the Next Gen-eration of Scientists from the Cancer Research Society. JLX is supported by a CIHR – Frederick Banting and Charles Best Canada Graduate Scholarship. The funding agencies had no role in the study design, data collection and inter-pretation, or the decision to submit the work for publication.",
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N2 - Mitochondria underpin metabolism, bioenergetics, signalling, development and cell death in eukaryotes. Most of the ~1,000 yeast mitochondrial proteins are encoded in the nucleus and synthesised as precursors in the cytosol, with mitochondrial import facilitated by molecular chaperones. Here, we focus on the Hsp40 chaperone Ydj1 in the fungal pathogen Candida albicans, finding that it is localised to both the cytosol and outer mitochondrial membrane, and is required for cellular stress responses and for filamentation, a key virulence trait. Mapping the Ydj1 protein interaction network highlighted connections with co-chaperones and regulators of filamentation. Furthermore, the mitochondrial processing peptidases Mas1 and Mas2 were highly enriched for interaction with Ydj1. Additional analysis demonstrated that loss of MAS1, MAS2 or YDJ1 perturbs mitochondrial morphology and function. Deletion of YDJ1 impairs import of Su9, a protein that is cleaved to a mature form by Mas1 and Mas2. Thus, we highlight a novel role for Ydj1 in cellular morphogenesis, stress responses, and mitochondrial import in the fungal kingdom.

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