An essential, kinetoplastid-specific GDP-Fuc: β-D-Gal α-1,2-fucosyltransferase is located in the mitochondrion of Trypanosoma brucei

• DOI: 10.7554/elife.70272
• Publication Date: 2021-08-19T14:00:15Z
• Authors: Giulia Bandini; Sebastian Damerow; Maria Lucia Sempa...; Hongjie Guo; Angela Mehlert; Jose Carlos Pared...; Stephen Beverley; Michael AJ Ferguson
• Keywords: 0301 basic medicine; 570; Trypanosoma; fucosyltranferase; Galactoside 2-alpha-L-fucosyltransferase; QH301-705.5; Science; Trypanosoma brucei brucei; 610; Gene Expression Regulation, Enzymologic; name=General Immunology and Microbiology; 03 medical and health sciences; glycobiology; Biochemistry and Chemical Biology; /dk/atira/pure/subjectarea/asjc/2800/2800; name=General Biochemistry,Genetics and Molecular Biology; /dk/atira/pure/subjectarea/asjc/2400/2400; Humans; Amino Acid Sequence; Biology (General); Cloning, Molecular; Phylogeny; 0303 health sciences; /dk/atira/pure/subjectarea/asjc/1300/1300; Q; R; name=General Neuroscience; Fucosyltransferases; Mitochondria; mitochondria; Medicine; kinetoplastid

Fucose is a common component of eukaryotic cell-surface glycoconjugates, generally added by Golgi-resident fucosyltransferases. Whereas fucosylated glycoconjugates are rare in kinetoplastids, the biosynthesis of the nucleotide sugar GDP-Fuc has been shown to be essential in Trypanosoma brucei. Here we show that the single identifiable T. brucei fucosyltransferase (TbFUT1) is a GDP-Fuc: β-D-galactose α-1,2-fucosyltransferase with an apparent preference for a Galβ1,3GlcNAcβ1-O-R acceptor motif. Conditional null mutants of TbFUT1 demonstrated that it is essential for both the mammalian-infective bloodstream form and the insect vector-dwelling procyclic form. Unexpectedly, TbFUT1 was localized in the mitochondrion of T. brucei and found to be required for mitochondrial function in bloodstream form trypanosomes. Finally, the TbFUT1 gene was able to complement a Leishmania major mutant lacking the homologous fucosyltransferase gene (Guo et al., 2021). Together these results suggest that kinetoplastids possess an unusual, conserved and essential mitochondrial fucosyltransferase activity that may have therapeutic potential across trypanosomatids.