Sorice Maurizio, Mattei Vincenzo, Matarrese Paola, Garofalo Tina, Tinari Antonella, Gambardella Lucrezia, Ciarlo Laura, Manganelli Valeria, Tasciotti Vincenzo, Misasi Roberta, Malorni Walter
Commun Integr Biol. 2012 Mar 1;5(2):217-9. doi: 10.4161/cib.19145.
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 (PrP(C)), 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.
基于脂筏的生化性质，其由糖鞘脂、胆固醇和信号蛋白组成，有人提出它们是导致CD95/Fas触发凋亡的亚细胞混合活动复杂框架的一部分。我们证明，在CD95/Fas触发后，细胞朊蛋白（PrP(C)）作为脂筏的典型成分，通过内质网（ER）-线粒体相关膜（MAM）和微管网络重新分布到线粒体样脂筏微结构域。脂筏样微结构域似乎参与一系列细胞内功能，如：（1）参与细胞死亡执行途径的膜“翻转”；（2）细胞器重塑；（3）蛋白质向线粒体的募集；（4）线粒体氧化磷酸化和ATP生成。总之，我们认为脂筏成分可在凋亡执行的三个不同水平发挥其调节活性：（1）在质膜上的死亡诱导信号复合物（DISC）形成中；（2）在细胞质细胞器的细胞内重新分布中；（3）在与凋亡执行相关的线粒体结构和功能修饰中。
