Coupling of lysosomal and mitochondrial membrane permeabilization in trypanolysis by APOL1

Vanwalleghem, Gilles, Fontaine, Frederic, Lecordier, Laurence, Tebabi, Patricia, Klewe, Kristoffer, Nolan, Derek P., Yamaryo-Botte, Yoshiki, Botte, Cyrille, Kremer, Anneke, Burkard, Gabriela S., Rassow, Joachim, Roditi, Isabel, Perez-Morga, David and Pays, Etienne (2015) Coupling of lysosomal and mitochondrial membrane permeabilization in trypanolysis by APOL1. Nature Communications, 6 8078: 1-10. doi:10.1038/ncomms9078


Author Vanwalleghem, Gilles
Fontaine, Frederic
Lecordier, Laurence
Tebabi, Patricia
Klewe, Kristoffer
Nolan, Derek P.
Yamaryo-Botte, Yoshiki
Botte, Cyrille
Kremer, Anneke
Burkard, Gabriela S.
Rassow, Joachim
Roditi, Isabel
Perez-Morga, David
Pays, Etienne
Title Coupling of lysosomal and mitochondrial membrane permeabilization in trypanolysis by APOL1
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2015-08-26
Year available 2015
Sub-type Article (original research)
DOI 10.1038/ncomms9078
Open Access Status DOI
Volume 6
Issue 8078
Start page 1
End page 10
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted 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.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Biomedical Sciences Publications
 
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