A broadly active fucosyltransferase LmjFUT1 whose mitochondrial localization and activity are essential in parasitic <i>Leishmania</i>
Hongjie Guo, Sebastian Damerow, Luciana Penha, Stefanie K. Menzies, Gloria Polanco, Hicham Zegzouti, Michael A. J. Ferguson, Stephen M. Beverley
Abstract
Significance Abundant surface glycoconjugates play key roles in the infectious cycle of protozoan parasites including Leishmania . Through defining biosynthetic pathways, we identified a fucosyltransferase FUT1 localized to the parasite mitochondrion, an atypical compartment for glycosyltransferases. FUT1 was essential for normal growth, requiring both mitochondrial localization and enzymatic activity. Loss of FUT1 in a single rare segregant ( fut1 s ) showed extensive mitochondrial defects. Enzymatic tests showed FUT1 could fucosylate glycan and peptide substrates in vitro, although as yet the native substrate(s) are unknown. Trypanosomatid mitochondrial FUT1s may offer a facile system in the future for probing mitochondrial glycosylation in a setting uncomplicated by multiple isoforms targeted to diverse compartments, and its essentiality renders it an attractive chemotherapeutic target for these deadly parasites.