The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress.
The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress.
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DOI：
10.1016/j.cmet.2018.06.008
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发表时间：
2018-09-04
期刊：
影响因子：
29
通讯作者：
Lee C
中科院分区：
文献类型：
--
作者：
Kim KH;Son JM;Benayoun BA;Lee C
细胞内稳态是通过线粒体和细胞核之间的通讯来协调的，线粒体和细胞核是各自拥有自己基因组的细胞器。虽然线粒体基因组由核中编码的因子调控，但目前尚不清楚核基因组是否受线粒体DNA中编码的因子主动控制。在这里，我们证明了MOTS-c，一种编码在线粒体基因组中的多肽，在代谢应激后以5‘-腺苷一磷酸激活蛋白激酶(AMPK)依赖的方式移位到细胞核并调节核基因的表达。在细胞核中，MOTS-c调控一系列响应葡萄糖限制的基因，包括那些含有抗氧化反应元件(ARE)的基因，并与ARE调节应激反应的转录因子相互作用，如核因子红系2相关因子2(NFE2L2/NRF2)。我们的发现表明，线粒体和核基因组共同进化，为相互交叉调节的因子独立编码，这表明有丝分裂通讯在基因上是整合的。线粒体基因组受核内编码因子的调节。Kim等人。现在表明，反过来，线粒体编码的多肽mots-c可以动态地移位到细胞核，以响应代谢应激，并调节适应性核基因的表达。他们的发现表明，有丝分裂通讯在基因上是整合的。
Cellular homeostasis is coordinated through communication between mitochondria and the nucleus, organelles that each possess their own genomes. Whereas the mitochondrial genome is regulated by factors encoded in the nucleus, the nuclear genome is currently not known to be actively controlled by factors encoded in the mitochondrial DNA. Here, we show that MOTS-c, a peptide encoded in the mitochondrial genome, translocates to the nucleus and regulates nuclear gene expression following metabolic stress in a 5′-adenosine mono-phosphate-activated protein kinase (AMPK)-dependent manner. In the nucleus, MOTS-c regulated a broad range of genes in response to glucose restriction, including those with antioxidant response elements (ARE), and interacted with ARE-regulating stress-responsive transcription factors, such as nuclear factor erythroid 2-related factor 2 (NFE2L2/NRF2). Our findings indicate that the mitochondrial and nuclear genomes co-evolved to independently encode for factors to cross-regulate each other, suggesting that mitonuclear communication is genetically integrated. The mitochondrial genome is regulated by factors encoded in the nucleus. Kim et al. now show that, reciprocally, MOTS-c, a mitochondrial-encoded peptide, can dynamically translocate to the nucleus in response to metabolic stress and regulate adaptive nuclear gene expression. Their findings suggest that mitonuclear communication is genetically integrated.
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