Identification of trypanosomatid PEX19: functional characterization reveals impact on cell growth and glycosome size and number

Mol Biochem Parasitol. 2005 Jul;142(1):47-55. doi: 10.1016/j.molbiopara.2005.03.008. Epub 2005 Apr 7.


Glycosomes are peroxisome-like organelles present in trypanosomatid pathogens. These organelles compartmentalize glycolysis, among other reactions, and are essential in both bloodstream and procyclic form Trypanosoma brucei. Peroxins (PEXs) are proteins necessary for biogenesis of peroxisomes and glycosomes. In each assembled trypanosomatid genome, we identified a predicted protein with approximately 20% sequence identity to human PEX19, a protein required for insertion of peroxisomal membrane proteins (PMPs) into the membrane. Functional analysis demonstrated that these proteins are indeed PEX19 orthologues. Like other PEX19s, T. brucei and Leishmania major PEX19 GFP fusion proteins are predominantly cytosolic. We further showed that LmPEX19 interacts with the glycosomal membrane protein PEX2 in the yeast two-hybrid system. Partial knockdown of TbPEX19 slowed parasite growth, particularly when glucose was present. Immunofluorescence and electron microscopic studies revealed biogenesis defect as evidenced by a sharp reduction in the number of glycosomes. Surprisingly, a four-fold increase in the size of the remaining glycosomes was observed. We propose that this phenotype of fewer but larger glycosomes results from the reduction in import of glycosomal membrane proteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Glycolysis
  • Humans
  • Leishmania major / genetics
  • Leishmania major / growth & development*
  • Leishmania major / metabolism
  • Membrane Proteins* / chemistry
  • Membrane Proteins* / genetics
  • Membrane Proteins* / metabolism
  • Molecular Sequence Data
  • Peroxisomal Biogenesis Factor 2
  • Peroxisomes / metabolism*
  • Protozoan Proteins* / chemistry
  • Protozoan Proteins* / genetics
  • Protozoan Proteins* / metabolism
  • Sequence Alignment
  • Trypanosoma brucei brucei / genetics
  • Trypanosoma brucei brucei / growth & development*
  • Trypanosoma brucei brucei / metabolism


  • Membrane Proteins
  • PEX2 protein, human
  • Protozoan Proteins
  • Peroxisomal Biogenesis Factor 2
  • PEX19 protein, human