Journal ArticleDOI
A broadly active fucosyltransferase LmjFUT1 whose mitochondrial localization and activity are essential in parasitic Leishmania.
Hongjie Guo,Sebastian Damerow,Luciana Penha,Stefanie Menzies,Gloria Polanco,Hicham Zegzouti,Michael A. J. Ferguson,Stephen M. Beverley +7 more
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TLDR
Guo et al. as mentioned in this paper showed that α 1-2 fucosyltransferase encoded by FUT1 localized to the mitochondrion is essential for normal growth and mitochondrial function.Abstract:
Glycoconjugates play major roles in the infectious cycle of the trypanosomatid parasite Leishmania While GDP-Fucose synthesis is essential, fucosylated glycoconjugates have not been reported in Leishmania major [H. Guo et al., J. Biol. Chem. 292, 10696-10708 (2017)]. Four predicted fucosyltransferases appear conventionally targeted to the secretory pathway; SCA1/2 play a role in side-chain modifications of lipophosphoglycan, while gene deletion studies here showed that FUT2 and SCAL were not essential. Unlike most eukaryotic glycosyltransferases, the predicted α 1-2 fucosyltransferase encoded by FUT1 localized to the mitochondrion. A quantitative "plasmid segregation" assay, expressing FUT1 from the multicopy episomal pXNG vector in a chromosomal null ∆fut1 - background, established that FUT1 is essential. Similarly, "plasmid shuffling" confirmed that both enzymatic activity and mitochondrial localization were required for viability, comparing import-blocked or catalytically inactive enzymes, respectively. Enzymatic assays of tagged proteins expressed in vivo or of purified recombinant FUT1 showed it had a broad fucosyltransferase activity including glycan and peptide substrates. Unexpectedly, a single rare ∆fut1 - segregant (∆fut1 s ) was obtained in rich media, which showed severe growth defects accompanied by mitochondrial dysfunction and loss, all of which were restored upon FUT1 reexpression. Thus, FUT1 along with the similar Trypanosoma brucei enzyme TbFUT1 [G. Bandini et al., bioRxiv, https://www.biorxiv.org/content/10.1101/726117v2 (2021)] joins the eukaryotic O-GlcNAc transferase isoform as one of the few glycosyltransferases acting within the mitochondrion. Trypanosomatid mitochondrial FUT1s may offer a facile system for probing mitochondrial glycosylation in a simple setting, and their essentiality for normal growth and mitochondrial function renders it an attractive target for chemotherapy of these serious human pathogens.read more
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An essential, kinetoplastid-specific GDP-Fuc: β-D-Gal α-1,2-fucosyltransferase is located in the mitochondrion of Trypanosoma brucei.
Giulia Bandini,Sebastian Damerow,Maria Lucia Sempaio Guther,Hongjie Guo,Angela Mehlert,Jose Carlos Paredes Franco,Stephen M. Beverley,Michael A. J. Ferguson +7 more
TL;DR: Guo et al. as discussed by the authors showed that the single identifiable T. brucei fucosyltransferase (TbFUT1) is a GDP-Fuc: β-D-galactose α-1,2-fucosytransferase with an apparent preference for a Galβ1,3GlcNAcβ1-O-R acceptor motif.
Journal ArticleDOI
Perchlorate‐specific proteomic stress responses of <scp> <i>Debaryomyces hansenii</i> </scp> could enable microbial survival in Martian brines
TL;DR: In this article , the perchlorate-specific stress responses of the halotolerant yeast Debaryomyces hansenii and compare these to generally known salt stress adaptations were investigated, and the responses to NaCl and NaClO4 -induced stresses share many common metabolic features, for example, signalling pathways, elevated energy metabolism, or osmolyte biosynthesis.
Journal ArticleDOI
Mitochondria inter-organelle relationships in cancer protein aggregation
TL;DR: In this paper , a review aims to gather the current knowledge about the complex liaison between mitochondria, ER, and lysosomes in facing proteotoxic stress and protein aggregation, highlighting both causes and consequences.
Posted ContentDOI
Perchlorate-Specific Proteomic Stress Responses of Debaryomyces hansenii Could Enable Microbial Survival in Martian Brines
Jacob Heinz,Joerg Doellinger,Deborah Maus,Andy Schneider,Peter Lasch,Hans-Peter Grossart,Dirk Schulze-Makuch +6 more
TL;DR: The first proteomic investigation on the perchlorate-specific stress responses of the halotolerant yeast Debaryomyces hansenii is presented and it is found that the responses to NaCl and NaClO4-induced stresses share many common metabolic features, e.g., signaling pathways, elevated energy metabolism, or osmolyte biosynthesis.
Journal ArticleDOI
Expanded Proteomic Survey of the Human Parasite Leishmania major Focusing on Changes in Null Mutants of the Golgi GDP-Mannose/Fucose/Arabinopyranose Transporter LPG2 and of the Mitochondrial Fucosyltransferase FUT1
TL;DR: In this paper , the authors leverage an ultradeep proteomic approach to improve their understanding of two virulenceassociated genes in Leishmania, encoding the Golgi mannose/arabinopyranose/fucose nucleotide-sugar transporter (LPG2) and the mitochondrial fucosyltransferase (FUT1).
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