Mitochondrial respiratory deficiencies signal up-regulation of genes for heat shock proteins
Mitochondrial respiratory deficiencies signal up-regulation of genes for heat shock proteins
复制标题
DOI：
10.1074/jbc.m400640200
复制
发表时间：
2004-05-14
影响因子：
4.8
通讯作者：
Newton, KJ
中科院分区：
文献类型：
--
作者：
Kuzmin, EV;Karpova, OV;Newton, KJ
线粒体功能障碍的后果不仅限于氧化应激的发展或细胞凋亡的启动，而且可以导致应激耐受的建立。使用玉米线粒体突变体，我们表明，永久性线粒体缺陷触发新的钙离子非依赖性信号通路，导致组成型表达的基因的分子伴侣，热休克蛋白（HSP）的不同类别。激活热休克蛋白基因的信号似乎源于线粒体跨膜电位的降低。在瞬时测定中，线粒体膜去极化后，线粒体热休克蛋白的基因诱导比胞质热休克蛋白发生得更快。我们还表明，在线虫线虫的hsp基因的转录可以诱导核呼吸基因的RNA干扰。在这两种生物体中，热休克蛋白基因对线粒体损伤的反应与对热休克的反应不同，并且与氧化应激无关。因此，细胞核信号传导表达热休克蛋白基因网络显然是一个广泛的逆行机制，以促进细胞防御和生存。
The consequences of mitochondrial dysfunction are not limited to the development of oxidative stress or initiation of apoptosis but can result in the establishment of stress tolerance. Using maize mitochondrial mutants, we show that permanent mitochondrial deficiencies trigger novel Ca2+-independent signaling pathways, leading to constitutive expression of genes for molecular chaperones, heat shock proteins (HSPs) of different classes. The signaling to activate hsp genes appears to originate from a reduced mitochondrial transmembrane potential. Upon depolarization of mitochondrial membranes in transient assays, gene induction for mitochondrial HSPs occurred more rapidly than that for cytosolic HSPs. We also demonstrate that in the nematode Caenorhabditis elegans transcription of hsp genes can be induced by RNA interference of nuclear respiratory genes. In both organisms, activation of hsp genes in response to mitochondrial impairment is distinct from their responses to heat shock and is not associated with oxidative stress. Thus, mitochondria-to-nucleus signaling to express a hsp gene network is apparently a widespread retrograde mechanism to facilitate cell defense and survival.