Dialogue between E-coli free radical pathways and the mitochondria of C-elegans
Dialogue between E-coli free radical pathways and the mitochondria of C-elegans
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DOI：
10.1073/pnas.1517448112
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发表时间：
2015-10-06
影响因子：
11.1
通讯作者：
Ruvkun, Gary
中科院分区：
文献类型：
--
作者：
Govindan, J. Amaranath;Jayamani, Elamparithi;Ruvkun, Gary
微生物世界给动物带来了复杂的机会和危险，动物已经针对微生物意图的暗示制定了监视和响应策略。我们在这里表明，线虫秀丽隐杆线虫的线粒体稳态反应途径对激活自由基解毒途径的大肠杆菌突变作出反应。大肠杆菌中的额外突变可能会抑制线虫线粒体反应的激活，这表明线虫会对大肠杆菌的产物做出反应，以预测对其线粒体的挑战。在已知介导线粒体防御的 50 个线虫基因失活中，我们发现线虫对产生自由基的大肠杆菌突变体的反应需要 7 个基因，其中包括 bZip 转录因子 atfs-1（与应激相关的激活转录因子）。 atfs-1 功能丧失突变体对产生自由基的大肠杆菌突变体的作用具有部分抵抗力，但在野生型大肠杆菌上生长的组成型活性 atfs-1 突变体不适当地激活了通常由大肠杆菌自由基途径突变体诱导的线粒体反应模式。来自产生自由基的大肠杆菌突变体的羰基化蛋白可能直接激活 ATFS-1/bZIP 转录因子以诱导线粒体应激反应：用 H2O2 处理的大肠杆菌喂养线虫会诱导线粒体未折叠蛋白反应，而肠道肽转运蛋白的抑制部分抑制了线虫对自由基受损的大肠杆菌的反应。
The microbial world presents a complex palette of opportunities and dangers to animals, which have developed surveillance and response strategies to hints of microbial intent. We show here that the mitochondrial homeostatic response pathway of the nematode Caenorhabditis elegans responds to Escherichia coli mutations that activate free radical detoxification pathways. Activation of C. elegans mitochondrial responses could be suppressed by additional mutations in E. coli, suggesting that C. elegans responds to products of E. coli to anticipate challenges to its mitochondrion. Out of 50 C. elegans gene inactivations known to mediate mitochondrial defense, we found that 7 genes were required for C. elegans response to a free radical producing E. coli mutant, including the bZip transcription factor atfs-1 (activating transcription factor associated with stress). An atfs-1 loss-of-function mutant was partially resistant to the effects of free radical-producing E. coli mutant, but a constitutively active atfs-1 mutant growing on wild-type E. coli inappropriately activated the pattern of mitochondrial responses normally induced by an E. coli free radical pathway mutant. Carbonylated proteins from free radical-producing E. coli mutant may directly activate the ATFS-1/bZIP transcription factor to induce mitochondrial stress response: feeding C. elegans with H2O2-treated E. coli induces the mitochondrial unfolded protein response, and inhibition of a gut peptide transporter partially suppressed C. elegans response to free radical damaged E. coli.