Leishmania donovani iron superoxide dismutase A is targeted to the mitochondria by its N-terminal positively charged amino acids.
Many reports have shown that Leishmania species are susceptible to reactive oxygen species (ROS) and reactive nitrogen species (RNS)-mediated killing. The superoxide dismutase (SOD) is one of the antioxidant defense enzymes important for parasite survival through its detoxification of superoxide into hydrogen peroxide and oxygen. The mitochondria produce numerous superoxide radicals as a by-product of cellular respiration and hence targeting of SODs to the mitochondria is critical in maintaining healthy mitochondria. This study examines the characteristic determinants for mitochondrial localization of Leishmania donovani FeSODA. We show that FeSODA is localized to the mitochondria and that the N-terminal 31 amino acid extension is important for its localization. Interestingly, further dissection of the 31 amino acid extension revealed that the first 8 amino acids of the FeSODA protein are sufficient for targeting to the mitochondria. In addition, we found that the four basic amino acid residues contained within the N-terminal extension are also important for targeting. These studies highlight important features of mitochondrial targeting sequences in kinetoplastids.
Getachew
Fitsum
F
Department of Biological Sciences, University of Calgary, 2500 University Dr. NW, Calgary, Alberta T2N 1N4, Canada.
Gedamu
Lashitew
L
D000595:Amino Acid Sequence; D000818:Animals; D019677:Artificial Gene Fusion; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D057927:Hydrophobic and Hydrophilic Interactions; D007893:Leishmania donovani / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000737:chemistry / Q000201:enzymology*; D008969:Molecular Sequence Data; D021382:Protein Sorting Signals / Q000235:genetics; D021381:Protein Transport; D013482:Superoxide Dismutase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D021382:Protein Sorting Signals; D049452:Green Fluorescent Proteins; D013482:Superoxide Dismutase