Coupling of lysosomal and mitochondrial membrane permeabilization in trypanolysis by APOL1.
Citation:
Vanwalleghem G, Fontaine F, Lecordier L, Tebabi P, Klewe K, Nolan DP, Yamaryo-Botté Y, Botté C, Kremer A, Burkard GS, Rassow J, Roditi I, Pérez-Morga D, Pays E.(, Coupling of lysosomal and mitochondrial membrane permeabilization in trypanolysis by APOL1., Nature Communications, 6, 2015, 8078 - 8088Download Item:
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
Tb
EndoG endonuclease to the nucleus. APOL1 is associated with the
kinesin
Tb
KIFC1, 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 (
Tb
MFNL). 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
Tb
KIFC1-mediated transport of APOL1 from endolysosomal
membranes to the mitochondrion
Sponsor
Grant Number
Science Foundation Ireland (SFI for RF)
Wellcome Trust
Author's Homepage:
http://people.tcd.ie/denolanDescription:
PUBLISHED
Author: NOLAN, DEREK
Type of material:
Journal ArticleCollections
Series/Report no:
Nature Communications;6;
Availability:
Full text availableSubject (TCD):
Immunology, Inflammation & InfectionMetadata
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