@article{fdi:010067709,
  title = {{F}unctional divergence of {SIR}2 orthologs between trypanosomatid parasites},
  author = {{V}ergnes, {B}aptiste and {G}azanion, {E}lodie and {G}rentzinger, {T}.},
  editor = {},
  language = {{ENG}},
  abstract = {{SIR}2 proteins are {NAD}+-dependent deacetylases involved in epigenetic control of gene expression and metabolic regulation through post-translational modification of diverse target proteins. {I}n pathogens, these enzymes are considered as attractive drug targets involved in key aspects of the infectious cycle. {L}eishmania infantum {L}i{SIR}2rp1 was among the first non-nuclear and essential {SIR}2 deacetylases described in eukaryotes. {H}ere, we show that the two other {L}i{SIR}2rp2 and {L}i{SIR}rp3 paralogs are both located in mitochondria. {G}ene deletion experiments show that {L}i{SIR}2rp3 is not required for parasite survival. {S}urprisingly, multiple extrachromosomal amplicons bearing the {L}i{SIR}2rp2 gene are constitutively produced in wild type strains. {C}onsequently, a knockout of this gene could not be obtained, even after episomal rescue experiments. {W}e further provide genetic and biochemical evidence showing that {SIR}2rp2 protein directly affects parasite proliferation in relation to {NAD}+ bioavailability. {T}ogether, these results highlight unexpected genus-specific divergence of the {SIR}2 machinery among trypanosomatid parasites.},
  keywords = {{L}eishmania ; {SIR}2 ; {NAD}(+) ; {A}mplicons},
  booktitle = {},
  journal = {{M}olecular and {B}iochemical {P}arasitology},
  volume = {207},
  numero = {},
  pages = {96--101},
  ISSN = {0166-6851},
  year = {2016},
  DOI = {10.1016/j.molbiopara.2016.06.004},
  URL = {https://www.documentation.ird.fr/hor/fdi:010067709},
}