FUNCTIONAL IDENTIFICATION OF A LEISHMANIA GENE-RELATED TO THE PEROXIN-2 GENE REVEALS COMMON ANCESTRY OF GLYCOSOMES AND PEROXISOMES

Glycosomes are membrane-bounded microbody organelles that compartmenta lize glycolysis as well as other important metabolic processes in tryp anosomatids, The compartmentalization of these enzymatic reactions is hypothesized to play a crucial role in parasite physiology, Although t he metabolic role of glycosomes differs substantially from that of the peroxisomes that are found in other eukaryotes, similarities in signa ls targeting proteins to these organelles suggest that glycosomes and peroxisomes may have evolved from a common ancestor, To examine this h ypothesis, as well as gain insights into the function of the glycosome , we used a positive genetic selection procedure to isolate the first Leishmania mutant (gim1-1 [glycosome import] mutant) with a defect in the import of glycosomal proteins, The mutant retains glycosomes but m islocalizes a subset glycosomal proteins to the cytoplasm, Unexpectedl y, the gim1-1 mutant lacks lipid bodies, suggesting a heretofore unkno wn role of the glycosome. We used genetic approaches to identify a gen e, GIM1, that is able to restore import and lipid bodies, A nonsense m utation was found in one allele of this gene in the mutant line, The p redicted Gim1 protein is related the peroxin 2 family of integral memb rane proteins, which are required for peroxisome biogenesis, The simil arities in sequence and function provide strong support for the common origin model of glycosomes and peroxisomes. The novel phenotype of gi m1-1 and distinctive role of Leishmania glycosomes suggest that future studies of this system will provide a new perspective on microbody bi ogenesis and function.