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Coupling of lysosomal and mitochondrial membrane permeabilization in trypanolysis by APOL1

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Abstract
Humans resist infection by the African parasite Trypanosoma brucei owing to the trypanolytic activity of the serum apolipoprotein L1 (APOL1). Following uptake by endocytosis in the parasite, APOL1 forms pores in endolysosomal membranes and triggers lysosome swelling. Here we show that APOL1 induces both lysosomal and mitochondrial membrane permeabilization (LMP and MMP). Trypanolysis coincides with MMP and consecutive release of the mitochondrial TbEndoG endonuclease to the nucleus. APOL1 is associated with the kinesin TbKIFC1, of which both the motor and vesicular trafficking VHS domains are required for MMP, but not for LMP. The presence of APOL1 in the mitochondrion is accompanied by mitochondrial membrane fenestration, which can be mimicked by knockdown of a mitochondrial mitofusin-like protein (TbMFNL). The BH3-like peptide of APOL1 is required for LMP, MMP and trypanolysis. Thus, trypanolysis by APOL1 is linked to apoptosis-like MMP occurring together with TbKIFC1-mediated transport of APOL1 from endolysosomal membranes to the mitochondrion.
Keywords
HUMAN SERUM, AFRICAN TRYPANOSOMES, TRYPANOSOMA-BRUCEI, PROGRAMMED CELL-DEATH, ENDONUCLEASE-G, RESISTANCE, VACUOLES, FISSION, YEAST, BAX

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MLA
Vanwalleghem, Gilles, et al. “Coupling of Lysosomal and Mitochondrial Membrane Permeabilization in Trypanolysis by APOL1.” NATURE COMMUNICATIONS, vol. 6, 2015, doi:10.1038/ncomms9078.
APA
Vanwalleghem, G., Fontaine, F., Lecordier, L., Tebabi, P., Klewe, K., Nolan, D. P., … Pays, E. (2015). Coupling of lysosomal and mitochondrial membrane permeabilization in trypanolysis by APOL1. NATURE COMMUNICATIONS, 6. https://doi.org/10.1038/ncomms9078
Chicago author-date
Vanwalleghem, Gilles, Frédéric Fontaine, Laurence Lecordier, Patricia Tebabi, Kristoffer Klewe, Derek P Nolan, Yoshiki Yamaryo-Botté, et al. 2015. “Coupling of Lysosomal and Mitochondrial Membrane Permeabilization in Trypanolysis by APOL1.” NATURE COMMUNICATIONS 6. https://doi.org/10.1038/ncomms9078.
Chicago author-date (all authors)
Vanwalleghem, Gilles, Frédéric Fontaine, Laurence Lecordier, Patricia Tebabi, Kristoffer Klewe, Derek P Nolan, Yoshiki Yamaryo-Botté, Cyrille Botté, Anna Kremer, Gabriela Schumann Burkard, Joachim Rassow, Isabel Roditi, David Pérez-Morga, and Etienne Pays. 2015. “Coupling of Lysosomal and Mitochondrial Membrane Permeabilization in Trypanolysis by APOL1.” NATURE COMMUNICATIONS 6. doi:10.1038/ncomms9078.
Vancouver
1.
Vanwalleghem G, Fontaine F, Lecordier L, Tebabi P, Klewe K, Nolan DP, et al. Coupling of lysosomal and mitochondrial membrane permeabilization in trypanolysis by APOL1. NATURE COMMUNICATIONS. 2015;6.
IEEE
[1]
G. Vanwalleghem et al., “Coupling of lysosomal and mitochondrial membrane permeabilization in trypanolysis by APOL1,” NATURE COMMUNICATIONS, vol. 6, 2015.
@article{7067211,
  abstract     = {{Humans resist infection by the African parasite Trypanosoma brucei owing to the trypanolytic activity of the serum apolipoprotein L1 (APOL1). Following uptake by endocytosis in the parasite, APOL1 forms pores in endolysosomal membranes and triggers lysosome swelling. Here we show that APOL1 induces both lysosomal and mitochondrial membrane permeabilization (LMP and MMP). Trypanolysis coincides with MMP and consecutive release of the mitochondrial TbEndoG endonuclease to the nucleus. APOL1 is associated with the kinesin TbKIFC1, of which both the motor and vesicular trafficking VHS domains are required for MMP, but not for LMP. The presence of APOL1 in the mitochondrion is accompanied by mitochondrial membrane fenestration, which can be mimicked by knockdown of a mitochondrial mitofusin-like protein (TbMFNL). The BH3-like peptide of APOL1 is required for LMP, MMP and trypanolysis. Thus, trypanolysis by APOL1 is linked to apoptosis-like MMP occurring together with TbKIFC1-mediated transport of APOL1 from endolysosomal membranes to the mitochondrion.}},
  articleno    = {{8078}},
  author       = {{Vanwalleghem, Gilles and Fontaine, Frédéric and Lecordier, Laurence and Tebabi, Patricia and Klewe, Kristoffer and Nolan, Derek P and Yamaryo-Botté, Yoshiki and Botté, Cyrille and Kremer, Anna and Schumann Burkard, Gabriela and Rassow, Joachim and Roditi, Isabel and Pérez-Morga, David and Pays, Etienne}},
  issn         = {{2041-1723}},
  journal      = {{NATURE COMMUNICATIONS}},
  keywords     = {{HUMAN SERUM,AFRICAN TRYPANOSOMES,TRYPANOSOMA-BRUCEI,PROGRAMMED CELL-DEATH,ENDONUCLEASE-G,RESISTANCE,VACUOLES,FISSION,YEAST,BAX}},
  language     = {{eng}},
  pages        = {{10}},
  title        = {{Coupling of lysosomal and mitochondrial membrane permeabilization in trypanolysis by APOL1}},
  url          = {{http://doi.org/10.1038/ncomms9078}},
  volume       = {{6}},
  year         = {{2015}},
}

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