Yeast AMID homologue Ndi1p displays respiration-restricted apoptotic activity and is involved in chronological aging
Yeast AMID homologue Ndi1p displays respiration-restricted apoptotic activity and is involved in chronological aging
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DOI：
10.1091/mbc.e05-04-0333
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发表时间：
2006-04-01
影响因子：
3.3
通讯作者：
Zhou, B
中科院分区：
文献类型：
--
作者：
Li, W;Sun, LB;Zhou, B
细胞凋亡诱导因子（AIF）和AIF同源线粒体相关死亡诱导因子（AMID）都是线粒体黄蛋白，可触发非半胱氨酸蛋白酶依赖性细胞凋亡。系统发育分析表明，这两种蛋白质从它们共同的原核生物祖先进化分化回来。与AIF相比，AMID的促凋亡性质及其作用方式尚不清楚。在这里，我们表明，酵母AMID同源内部NADH脱氢酶（NDI1），但不是外部的NADH脱氢酶（NDE1）的过表达，可以导致类凋亡的细胞死亡，这种影响可以通过增加呼吸抑制葡萄糖限制的媒体。这一结果表明，能量代谢的调节网络，特别是线粒体和细胞其余部分之间的串扰，参与了Ndi1p诱导的酵母细胞凋亡。NDI 1过表达的凋亡效应与线粒体中活性氧（ROS）的产生增加有关。此外，在sod2背景下的NDI1过表达导致可发酵和半发酵培养基中的细胞死亡。电子传递链中某些成分的中断可以抑制Ndi 1p过表达引起的生长抑制。最后，我们发现，NDI1或NDE1的破坏减少了ROS的产生，延长了酵母的时间寿命，伴随着生存适应性的丧失。Ndi1p诱导的细胞凋亡的这些研究结果的含义进行了讨论。
Apoptosis-inducing factor (AIF) and AIF-homologous mitochondrion-associated inducer of death (AMID) are both mitochondrial flavoproteins that trigger caspase-independent apoptosis. Phylogenetic analysis suggests that these two proteins evolutionarily diverge back from their common prokaryote ancestor. Compared with AIF, the proapoptotic nature of AMID and its mode of action are much less clarified. Here, we show that overexpression of yeast AMID homologue internal NADH dehydrogenase (NDI1), but not external NADH dehydrogenase (NDE1), can cause apoptosis-like cell death, and this effect can be repressed by increased respiration on glucose-limited media. This result indicates that the regulatory network of energy metabolism, in particular the cross-talk between mitochondria and the rest of the cell, is involved in Ndi1p-induced yeast cell apoptosis. The apoptotic effect of NDI1 overexpression is associated with increased production of reactive oxygen species (ROS) in mitochondria. In addition, NDI1 overexpression in sod2 background causes cell lethality in both fermentable and semifermentable media. Interruption of certain components in the electron transport chain can suppress the growth inhibition from Ndi1p overexpression. We finally show that disruption of NDI1 or NDE1 decreases ROS production and elongates the chronological life span of yeast, accompanied by the loss of survival fitness. Implication of these findings for Ndi1p-induced apoptosis is discussed.