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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.

Recruitment of cellular prion protein to mitochondrial raft-like microdomains contributes to apoptosis execution / Vincenzo, Mattei; P., Matarrese; Garofalo, Tina; A., Tinari; L., Gambardella; L., Ciarlo; Manganelli, Valeria; Tasciotti, Vincenzo; Misasi, Roberta; W., Malorni; Sorice, Maurizio. - In: MOLECULAR BIOLOGY OF THE CELL. - ISSN 1059-1524. - STAMPA. - 22:24(2011), pp. 4842-4853. [10.1091/mbc.e11-04-0348]

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