Down regulation of Tim50 in Trypanosoma brucei increases tolerance to oxidative stress

Molecular and Biochemical Parasitology
Marjorie FullertonMinu Chaudhuri

Abstract

Trypanosoma brucei, the causative agent for African trypanosomiasis, possesses a single mitochondrion that imports hundreds of proteins from the cytosol. However, the parasite only possesses a few homologs of the canonical protein translocases found in fungi and animals. We recently characterized a homolog of the translocase of the mitochondrial inner membrane, Tim50, in T. brucei. TbTim50 knockdown (KD) moderately reduced cell growth, decreased the mitochondrial membrane potential, and inhibited import of proteins into mitochondria. In contrast to Tim50 KD, we show here that TbTim50 overexpression (OE) increased the mitochondrial membrane potential as well as increased the production of cellular reactive oxygen species (ROS). Therefore, TbTim50 OE also inhibits cell growth. In addition, TbTim50 OE and KD cells showed different responses upon treatment with H2O2. Surprisingly, TbTim50 KD cells showed a greater tolerance to oxidative stress. Further analysis revealed that TbTim50 KD inhibits transition of cells from an early to late apoptotic stage upon exposure to increasing concentrations of H2O2. On the other hand TbTim50 OE caused cells to be in a pro-apoptotic stage and thus they underwent increased cell death upon H2O2 tre...Continue Reading

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Citations

Aug 21, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Shui-Ping GaoWei Jin
Aug 9, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xiao ChenZichun Hua
Jul 22, 2015·Antimicrobial Agents and Chemotherapy·Luis CarvalhoJosé M Pérez-Victoria
Aug 8, 2021·International Journal of Molecular Sciences·Minu ChaudhuriFidel Soto Gonzalez

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African trypanosomiasis, also known as sleeping sickness, is an insect-borne parasitic disease of humans and other animals. It is caused by protozoa of the species Trypanosoma brucei and almost invariably progresses to death unless treated. Discover the latest research on African trypanosomiasis here.