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Maurizio Sorice,
Vincenzo Mattei,
Paola Matarrese,
Tina Garofalo,
Antonella Tinari,
Lucrezia Gambardella,
Laura Ciarlo,
Valeria Manganelli,
Vincenzo Tasciotti,
Roberta Misasi,
Walter Malorni
Keywords:
apoptosis,
gangliosides,
microdomains,
mitochondria,
prion protein,
rafts,
scrambling
Abstract:
On the basis of the biochemical nature of lipid rafts, composed by glycosphingolipids, cholesterol and signaling proteins, it has been suggested that they are part of the complex framework of subcellular intermixing activities that lead to CD95/Fas-triggered apoptosis. We demonstrated that, following CD95/Fas triggering, cellular prion protein (PrPC), which represents a paradigmatic component of lipid rafts, was redistributed to mitochondrial raft-like microdomains via endoplasmic reticulum (ER)-mitochondria associated membranes (MAM) and microtubular network.
Raft-like microdomains appear to be involved in a series of intracellular functions, such as: (1) the membrane “scrambling” that participates in cell death execution pathways, (2) the remodeling of organelles, (3) the recruitment of proteins to the mitochondria; (4) the mitochondrial oxidative phosphorylation and ATP production.
In conclusion, we suggest that lipid raft components can exert their regulatory activity in apoptosis execution at three different levels: (1) in the DISC formation at the plasma membrane; (2) in the intracellular redistribution at cytoplasmic organelles, and, (3) in the structural and functional mitochondrial modifications associated with apoptosis execution.
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