Fzo1, a protein involved in mitochondrial fusion, inhibits apoptosis
Fzo1, a protein involved in mitochondrial fusion, inhibits apoptosis
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DOI：
10.1074/jbc.m408910200
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发表时间：
2004-12-10
影响因子：
4.8
通讯作者：
Tsujimoto, Y
中科院分区：
文献类型：
--
作者：
Sugioka, R;Shimizu, S;Tsujimoto, Y
线粒体的形态和生理学受融合和分裂过程的调节。据报道，某些形式的细胞凋亡与线粒体片段化有关。我们发现，参与线粒体融合的Fzo 1A/B（大鼠）蛋白的过表达，或Dnm 1（大鼠）/Drp 1（人）（线粒体分裂蛋白）的沉默，增加了健康细胞中的线粒体延长。凋亡刺激后，这些干预措施抑制线粒体断裂和细胞死亡，这表明线粒体融合/分裂的过程中可能发挥作用，在调节细胞凋亡。一致地，沉默Fzo 1A/B或Mfn 1/2（Fzo 1A/B的人类同源物）导致较短线粒体的增加和增强的凋亡性死亡。Fzo 1的过表达抑制细胞色素c的释放和Bax/巴克的激活，从构象变化和寡聚化评估。沉默Mfn或Drp 1分别引起线粒体对凋亡刺激的敏感性增加或降低。这些结果表明，参与线粒体融合/分裂的一些蛋白质在线粒体水平上调节凋亡性细胞死亡。
Mitochondrial morphology and physiology are regulated by the processes of fusion and fission. Some forms of apoptosis are reported to be associated with mitochondrial fragmentation. We showed that overexpression of Fzo1A/B ( rat) proteins involved in mitochondrial fusion, or silencing of Dnm1 (rat)/Drp1 (human) (a mitochondrial fission protein), increased elongated mitochondria in healthy cells. After apoptotic stimulation, these interventions inhibited mitochondrial fragmentation and cell death, suggesting that a process involved in mitochondrial fusion/fission might play a role in the regulation of apoptosis. Consistently, silencing of Fzo1A/B or Mfn1/2 (a human homolog of Fzo1A/B) led to an increase of shorter mitochondria and enhanced apoptotic death. Overexpression of Fzo1 inhibited cytochrome c release and activation of Bax/Bak, as assessed from conformational changes and oligomerization. Silencing of Mfn or Drp1 caused an increase or decrease of mitochondrial sensitivity to apoptotic stimulation, respectively. These results indicate that some of the proteins involved in mitochondrial fusion/fission modulate apoptotic cell death at the mitochondrial level.