Recruitment of cellular prion protein to mitochondrial raft-like microdomains contributes to apoptosis execution |
| |
Authors: | Mattei Vincenzo Matarrese Paola Garofalo Tina Tinari Antonella Gambardella Lucrezia Ciarlo Laura Manganelli Valeria Tasciotti Vincenzo Misasi Roberta Malorni Walter Sorice Maurizio |
| |
Institution: | Laboratory of Experimental Medicine and Environmental Pathology, Sabina Universitas, 02100 Rieti, Italy. |
| |
Abstract: | We examined the possibility that cellular prion protein (PrP(C)) plays a role in the receptor-mediated apoptotic pathway. We first found that CD95/Fas triggering induced a redistribution of PrP(C) to the mitochondria of T lymphoblastoid CEM cells via a mechanism that brings into play microtubular network integrity and function. In particular, we demonstrated that PrP(C) was redistributed to raft-like microdomains at the mitochondrial membrane, as well as at endoplasmic reticulum-mitochondria-associated membranes. Our in vitro experiments also demonstrated that, although PrP(C) had such an effect on mitochondria, it induced the loss of mitochondrial membrane potential and cytochrome c release only after a contained rise of calcium concentration. Finally, the involvement of PrP(C) in apoptosis execution was also analyzed in PrP(C)-small interfering RNA-transfected cells, which were found to be significantly less susceptible to CD95/Fas-induced apoptosis. Taken together, these results suggest that PrP(C) might play a role in the complex multimolecular signaling associated with CD95/Fas receptor-mediated apoptosis. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|