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Recruitment of cellular prion protein to mitochondrial raft-like microdomains contributes to apoptosis execution.
MedLine Citation:
PMID:  22031292     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
In this study we analyzed the possibility that cellular prion protein (PrP(C)) could play a role in 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 bring into play microtubular network integrity and function. In particular, we demonstrated that PrP(C) was redistributed to raft-like microdomains at mitochondrial membrane as well as at endoplasmic reticulum (ER)-mitochondria associated membranes (MAM). 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 citochrome C release only after a contained raise of calcium concentration. Finally, the involvement of PrP(C) in apoptosis execution was also analyzed in PrP(C)-siRNA transfected cells, which were found significantly less susceptible to CD95/Fas-induced apoptosis. Altogether, these results suggest that PrP(C) may play a role in the complex multimolecular signaling associated with CD95/Fas receptor-mediated apoptosis.
Authors:
Vincenzo Mattei; Paola Matarrese; Tina Garofalo; Antonella Tinari; Lucrezia Gambardella; Laura Ciarlo; Valeria Manganelli; Vincenzo Tasciotti; Roberta Misasi; Walter Malorni; Maurizio Sorice
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-26
Journal Detail:
Title:  Molecular biology of the cell     Volume:  -     ISSN:  1939-4586     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Laboratory of Experimental Medicine and Environmental Pathology, "Sabina Universitas", Rieti, Italy Section of Cell Aging and Degeneration, Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Rome, Italy Center of Integrated Metabolomics, Rome, Italy Department of Experimental Medicine, "Sapienza" University, Rome, Italy Department of Technology and Health, Istituto Superiore di Sanità, Rome, Italy San Raffaele Institute Sulmona, L'Aquila, Italy.
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