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Coupling of lysosomal and mitochondrial membrane permeabilization in trypanolysis by APOL1

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  • Gilles Vanwalleghem

    (Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles (ULB)
    Present address: Laboratory for Neural Circuits and Behaviour, School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia)

  • Frédéric Fontaine

    (Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles (ULB))

  • Laurence Lecordier

    (Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles (ULB))

  • Patricia Tebabi

    (Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles (ULB))

  • Kristoffer Klewe

    (Institute of Biochemistry and Pathobiochemistry, Ruhr-Universität Bochum)

  • Derek P. Nolan

    (Molecular Parasitology Group, School of Biochemistry and Immunology, Trinity College Dublin)

  • Yoshiki Yamaryo-Botté

    (Apicolipid Group, CNRS, Laboratoire Adaptation et Pathogénie des Microorganismes UMR5163/ Institut Albert Bonniot CRI Inserm/UJF U823, CNRS, Institut Jean Roget)

  • Cyrille Botté

    (Apicolipid Group, CNRS, Laboratoire Adaptation et Pathogénie des Microorganismes UMR5163/ Institut Albert Bonniot CRI Inserm/UJF U823, CNRS, Institut Jean Roget)

  • Anneke Kremer

    (IRC/VIB Bio Imaging Core, Gent)

  • Gabriela Schumann Burkard

    (Institute of Cell Biology, University of Bern)

  • Joachim Rassow

    (Institute of Biochemistry and Pathobiochemistry, Ruhr-Universität Bochum)

  • Isabel Roditi

    (Institute of Cell Biology, University of Bern)

  • David Pérez-Morga

    (Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles (ULB)
    Center for Microscopy and Molecular Imaging (CMMI), Université Libre de Bruxelles (ULB))

  • Etienne Pays

    (Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles (ULB)
    Walloon Excellence in Life sciences and Biotechnology (WELBIO), Wavre, Belgium)

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.

Suggested Citation

  • Gilles Vanwalleghem & Frédéric Fontaine & Laurence Lecordier & Patricia Tebabi & Kristoffer Klewe & Derek P. Nolan & Yoshiki Yamaryo-Botté & Cyrille Botté & Anneke Kremer & Gabriela Schumann Burkard &, 2015. "Coupling of lysosomal and mitochondrial membrane permeabilization in trypanolysis by APOL1," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9078
    DOI: 10.1038/ncomms9078
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