Coupling of lysosomal and mitochondrial membrane permeabilization in trypanolysis by APOL1

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 and Etienne Pays ()
Additional contact information
Gilles Vanwalleghem: Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles (ULB)
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)
Etienne Pays: Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles (ULB)

Nature Communications, 2015, vol. 6, issue 1, 1-10

Abstract: 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.

Date: 2015
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms9078 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9078

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms9078

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().