Cytosolic Peroxidases Protect the Lysosome of Bloodstream African Trypanosomes from Iron-Mediated Membrane Damage

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In many cell types, mitochondria are the main source of intracellular reactive oxygen species but iron-induced oxidative lysosomal damage has been described as well. African trypanosomes are the causative agents of human sleeping sickness and the cattle disease Nagana. The parasites are obligate extracellular pathogens that multiply in the bloodstream and body fluids of their mammalian hosts and as procyclic forms in their insect vector, the tsetse fly. Bloodstream Trypanosoma brucei in which the genes for cytosolic lipid hydroperoxide-detoxifying peroxidases have been knocked out undergo an extremely rapid membrane peroxidation and lyse within less than two hours when they are cultured without an exogenous antioxidant. Here we show that the primary site of intracellular damage is the single terminal lysosome of the parasites. Disintegration of the lysosome clearly precedes damage of the mitochondrion and parasite death. Iron, acquired by the endocytosis of iron-loaded host transferrin, induces cell lysis. Contrary to the cytosolic enzymes, the respective mitochondrial peroxidase is dispensable for both in vitro proliferation and mouse infectivity. This is the first report demonstrating that cytosolic thiol peroxidases are responsible for protecting the lysosome of a cell.

Vyšlo v časopise: Cytosolic Peroxidases Protect the Lysosome of Bloodstream African Trypanosomes from Iron-Mediated Membrane Damage. PLoS Pathog 10(4): e32767. doi:10.1371/journal.ppat.1004075
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004075

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