Compartmentation of enzymes in a microbody, the glycosome, is essential in Trypanosoma brucei.
All kinetoplastids contain membrane-bound microbodies known as glycosomes, in which several metabolic pathways including part of glycolysis are compartmentalized. Peroxin 2 is essential for the import of many proteins into the microbodies of yeasts and mammals. The PEX2 gene of Trypanosoma brucei was identified and its expression was silenced by means of tetracycline-inducible RNA interference. Bloodstream-form trypanosomes, which rely exclusively on glycolysis for ATP generation, died rapidly upon PEX2 depletion. Insect-form (procyclic) trypanosomes do not rely solely on glycolysis for ATP synthesis. PEX2 depletion in procyclic forms resulted in relocation of most tested matrix proteins to the cytosol, and these mutants also died. Compartmentation of microbody enzymes is therefore essential for survival of bloodstream and procyclic T. brucei. In contrast, yeasts and cultured mammalian cells grow normally in the absence of peroxisomal membranes unless placed on selective media.
Guerra-Giraldez
Cristina
C
Zentrum für Molekulare Biologie der Universität Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
Quijada
Luis
L
Clayton
Christine E
CE
D000818:Animals; D002451:Cell Compartmentation / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D005804:Genes, Lethal / Q000235:genetics; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis / Q000235:genetics; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D008830:Microbodies / Q000201:enzymology* / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics; D000074428:Peroxisomal Biogenesis Factor 2; D021381:Protein Transport / Q000235:genetics; D012330:RNA, Double-Stranded / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D014346:Trypanosoma brucei brucei / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D014353:Trypanosomiasis, African / Q000201:enzymology* / Q000469:parasitology
D008565:Membrane Proteins; C490455:PEX11A protein, human; C490453:PEX11B protein, human; C000614230:PEX2 protein, human; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D000074428:Peroxisomal Biogenesis Factor 2; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases