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Acta Physiologica 2012; Volume 206, Supplement 692
The 63rd National Congress of the Italian Physiological Society
9/21/2012-9/23/2012
Verona, Italy
TRANSPORTING CARGOES TO MITOCHONDRIA. A NOVEL INTRACELLULAR TRAFFICKING PATHWAY UNRAVELLED BY MEANS OF VACA TOXIN
Abstract number: O.46
SOMMI1 P, BOQUET2 P, RICCI1 V
1Dept Molecular Medicine, Univ. of Pavia Medical School, Pavia, Italy
2Dept Clinical Bacteriology, Univ. of Nice-Sophia Antipolis, Nice, France
Background & Aim: Poisons are chemical scalpels useful to dissect biological processes. Bacterial toxins (the most powerful natural poisons) greatly contributed to unravel basic mechanisms in cell biology. VacA toxin from Helicobacter pylori enters epithelial cells and reaches mitochondria where it triggers apoptosis. This study was aimed to investigate such an intracellular trafficking pathway.
Methods: Epithelial cell lines, variously transfected and/or drug-treated, were intoxicated with purified VacA. The intracellular trafficking of the toxin and its resulting effects were monitored by laser-scanning confocal microscopy (including time-lapse videomicroscopy).
Results: We found that VacA was first internalized in a tubulo-vesicular compartment located close to the plasma membrane. From such a compartment arose a subpopulation of early endosomes (EE) that underwent motility via the formation of actin comet tails at their surface. Actin-dependent motility of toxin-containing EE allowed their trafficking to the mitochondria, where VacA translocated. Disruption of F-actin filaments prevented VacA from reaching mitochondria and thus from causing apoptosis.
Conclusions: Our work provides evidence of an intracellular trafficking pathway through which cargoes can be transported to mitochondria via rocketing EE. Further studies are in progress to decipher whether cargo-containing EE stably dock with mitochondria or they transfer cargoes through a 'kiss-and-run' mechanism.
To cite this abstract, please use the following information:
Acta Physiologica 2012; Volume 206, Supplement 692 :O.46