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Trypanosomes and renal insufficiency: APOL1 induces a double permeabilization

Date:
August 27, 2015
Source:
Libre de Bruxelles, Université
Summary:
Scientists shed further light on the way human APOL1 kills the trypanosmoe.
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Scientists shed further light on the way human APOL1 kills the trypanosmoe.

The African trypanosome Trypanosoma brucei is a blood parasite capable of infecting many mammals. Humans are provided with natural immunity against infection through the activity of the protein apolipoprotein L1 (APOL1): captured via endocytosis, APOL1 forms pores in the lysosomal membrane, leading to the death of the trypanosome.

In a publication in the scientific journal Nature Communications, Prof Etienne Pays and his team from the ULB's Laboratory of Molecular Parasitology (Faculty of Science) sheds further light on the way human APOL1 kills the parasite. APOL1 does not just induce lysosomal membrane permeabilization. Once it has accomplished this, it is transported to the mitochondrion where it again induces membrane permeabilization. The subsequent release of a mitochondrial endonuclease into the nucleus leads to trypanolysis.

However, this defence mechanism is not infallible: two trypanosomes, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense manage to evade APOL1, and can infect humans with sleeping sickness. Two distinct mutations of APOL1 enable a number of West African populations to be immune to one of these trypanosomes. However, in 2010, Etienne Pays' laboratory proved that this evolutionary advantage went hand in hand with an increased risk of renal insufficiency. While the mechanism allowing these mutations of APOL1 to trigger renal pathology remains completely unknown, our new observations on the biology of APOL1 allow us to imagine how the disease could occur in human kidney cells and to develop new research hypotheses.


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Materials provided by Libre de Bruxelles, Université. Note: Content may be edited for style and length.


Journal Reference:

  1. Gilles Vanwalleghem, Frédéric Fontaine, Laurence Lecordier, Patricia Tebabi, Kristoffer Klewe, Derek P. Nolan, Yoshiki Yamaryo-Botté, Cyrille Botté, Anneke Kremer, Gabriela Schumann Burkard, Joachim Rassow, Isabel Roditi, David Pérez-Morga, Etienne Pays. Coupling of lysosomal and mitochondrial membrane permeabilization in trypanolysis by APOL1. Nature Communications, 2015; 6: 8078 DOI: 10.1038/ncomms9078

Cite This Page:

Libre de Bruxelles, Université. "Trypanosomes and renal insufficiency: APOL1 induces a double permeabilization." ScienceDaily. ScienceDaily, 27 August 2015. <www.sciencedaily.com/releases/2015/08/150827083540.htm>.
Libre de Bruxelles, Université. (2015, August 27). Trypanosomes and renal insufficiency: APOL1 induces a double permeabilization. ScienceDaily. Retrieved May 25, 2017 from www.sciencedaily.com/releases/2015/08/150827083540.htm
Libre de Bruxelles, Université. "Trypanosomes and renal insufficiency: APOL1 induces a double permeabilization." ScienceDaily. www.sciencedaily.com/releases/2015/08/150827083540.htm (accessed May 25, 2017).

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