Association of fission proteins with mitochondrial raft-like domains
Association of fission proteins with mitochondrial raft-like domains
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DOI：
10.1038/cdd.2009.208
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发表时间：
2010-06-01
影响因子：
12.4
通讯作者：
Sorice, M.
中科院分区：
文献类型：
--
作者：
Ciarlo, L.;Manganelli, V.;Sorice, M.
研究表明，受体介导的细胞凋亡涉及一系列亚细胞事件，包括线粒体的改变。死亡受体连接后线粒体膜电位的丧失允许导致细胞凋亡执行的致凋亡因子的释放。在这方面已经观察到了进一步重要的线粒体变化：线粒体重塑和分裂似乎是细胞死亡程序发生的先决条件。由于观察到脂筏，富含鞘糖脂的结构，可以参与受体介导的促凋亡刺激下被招募到线粒体的凋亡级联反应，我们决定分析这些微结构域在线粒体分裂中的可能意义。我们发现参与线粒体分裂过程的分子与这些结构域相关。特别是，虽然hFis 1是组成性包括在线粒体筏样结构域，发动蛋白样蛋白1被招募到这些结构域的CD 95/Fas触发。因此，例如通过抑制神经酰胺合酶来破坏筏，导致分裂分子募集到线粒体的损害、线粒体分裂的减少和细胞凋亡的显著减少。我们推测，在细胞凋亡刺激下，线粒体筏的分裂相关分子的募集可能在导致细胞器分裂的形态发生变化中发挥作用。Cell Death and Differentiation（2010）17，1047-1058; doi：10.1038/cdd.2009.208; 2010年1月15日在线发表
It was shown that receptor-mediated apoptosis involves a cascade of subcellular events including alterations of mitochondria. Loss of mitochondrial membrane potential that follows death receptor ligation allows the release of apoptogenic factors that result in apoptosis execution. Further important mitochondrial changes have been observed in this regard: mitochondrial remodeling and fission that appear as prerequisites for the occurrence of the cell death program. As it was observed that lipid rafts, glycosphingolipid-enriched structures, can participate in the apoptotic cascade being recruited to the mitochondria under receptor-mediated proapoptotic stimulation, we decided to analyze the possible implication of these microdomains in mitochondrial fission. We found that molecules involved in mitochondrial fission processes are associated with these domains. In particular, although hFis1 was constitutively included in mitochondrial raft-like domains, dynamin-like protein 1 was recruited to these domains on CD95/Fas triggering. Accordingly, the disruption of rafts, for example, by inhibiting ceramide synthase, leads to the impairment of fission molecule recruitment to the mitochondria, reduction of mitochondrial fission and a significant reduction of apoptosis. We hypothesize that under apoptotic stimulation the recruitment of fission-associated molecules to the mitochondrial rafts could have a role in the morphogenetic changes leading to organelle fission. Cell Death and Differentiation (2010) 17, 1047-1058; doi:10.1038/cdd.2009.208; published online 15 January 2010