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 compartmentalize glycolysis as well as other important metabolic processes in trypanosomatids. The compartmentalization of these enzymatic reactions is hypothesized to play a crucial role in parasite physiology. Although the metabolic role of glycosomes differs substantially from that of the peroxisomes that are found in other eukaryotes, similarities in signals targeting proteins to these organelles suggest that glycosomes and peroxisomes may have evolved from a common ancestor. To examine this hypothesis, 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 mislocalizes a subset glycosomal proteins to the cytoplasm. Unexpectedly, the gim1-1 mutant lacks lipid bodies, suggesting a heretofore unknown role of the glycosome. We used genetic approaches to identify a gene, GIM1, that is able to restore import and lipid bodies. A nonsense mutation was found in one allele of this gene in the mutant line. The predicted Gim1 protein is related the peroxin 2 family of integral membrane proteins, which are required for peroxisome biogenesis. The similarities in sequence and function provide strong support for the common origin model of glycosomes and peroxisomes. The novel phenotype of gim1-1 and distinctive role of Leishmania glycosomes suggest that future studies of this system will provide a new perspective on microbody biogenesis and function.
Flaspohler
J A
JA
Seattle Biomedical Research Institute, Washington 98109, USA.
Rickoll
W L
WL
Beverley
S M
SM
Parsons
M
M
D000595:Amino Acid Sequence; D000818:Animals; D018628:Gene Dosage; D017125:Genes, Protozoan / Q000235:genetics / Q000502:physiology*; D007893:Leishmania donovani / Q000235:genetics* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000235:genetics*; D008830:Microbodies / Q000378:metabolism / Q000648:ultrastructure; D008969:Molecular Sequence Data; D000074428:Peroxisomal Biogenesis Factor 2; D010802:Phylogeny; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D016053:RNA, Protozoan / Q000032:analysis; D015183:Restriction Mapping; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
C104437:GIM1 protein, Leishmania; D008565:Membrane Proteins; D015800:Protozoan Proteins; D012333:RNA, Messenger; D016053:RNA, Protozoan; D000074428:Peroxisomal Biogenesis Factor 2