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Recruitment of cellular prion protein to mitochondrial raft-like microdomains contributes to apoptosis execution

Vincenzo Mattei1, Paola Matarrese, Tina Garofalo

  • 1Laboratory of Experimental Medicine and Environmental Pathology, Sabina Universitas, 02100 Rieti, Italy.

Molecular Biology of the Cell
|October 28, 2011
PubMed

Insights

Cellular prion protein (PrP(C)) is involved in the CD95/Fas-mediated apoptosis pathway. PrP(C) redistribution to mitochondria promotes apoptosis, while its reduction increases cell resistance.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Immunology

Background:

  • The role of cellular prion protein (PrP(C)) in cellular signaling pathways remains incompletely understood.
  • Receptor-mediated apoptosis, particularly via CD95/Fas, is a critical process in cellular regulation and immune responses.

Purpose of the Study:

  • To investigate the potential involvement of PrP(C) in the CD95/Fas receptor-mediated apoptotic pathway.
  • To elucidate the subcellular localization and functional consequences of PrP(C) redistribution during apoptosis.

Main Methods:

  • Utilized T lymphoblastoid CEM cells for apoptosis induction studies.
  • Investigated PrP(C) redistribution upon CD95/Fas triggering using microscopy and biochemical assays.
  • Assessed mitochondrial membrane potential, calcium concentration, and cytochrome c release.
  • Employed small interfering RNA (siRNA) to reduce PrP(C) expression and evaluate apoptosis susceptibility.

Main Results:

  • CD95/Fas triggering induced PrP(C) redistribution to mitochondria, specifically to raft-like microdomains and ER-mitochondria-associated membranes.
  • PrP(C) redistribution to mitochondria promoted apoptosis by influencing mitochondrial membrane potential and cytochrome c release, contingent on calcium levels.
  • Cells with reduced PrP(C) expression (via siRNA) exhibited significantly lower susceptibility to CD95/Fas-induced apoptosis.

Conclusions:

  • Cellular prion protein (PrP(C)) plays a role in the execution phase of CD95/Fas receptor-mediated apoptosis.
  • PrP(C) localization to mitochondria is a key event in the signaling cascade leading to apoptosis.
  • These findings highlight PrP(C) as a potential modulator of programmed cell death.

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