Transcription factors CEP-1/p53 and CEH-23 collaborate with AAK-2/AMPK to modulate longevity in Caenorhabditis elegans.
Transcription factors CEP-1/p53 and CEH-23 collaborate with AAK-2/AMPK to modulate longevity in Caenorhabditis elegans.
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DOI：
10.1111/acel.12619
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发表时间：
2017-08
期刊：
影响因子：
7.8
通讯作者：
Lee SS
中科院分区：
文献类型：
--
作者：
Chang HW;Pisano S;Chaturbedi A;Chen J;Gordon S;Baruah A;Lee SS
线粒体电子传输链(ETC)功能下降长期以来一直与衰老和各种疾病有关。最近，在不同的生物中发现适度的线粒体ETC功能障碍可以延长寿命，这表明线粒体在决定寿命的过程中扮演着保守而复杂的角色。一些核转录因子已经被证明介导了与ETC部分损伤相关的寿命延长效应，这表明补偿转录反应是至关重要的。在本研究中，我们发现转录因子CEP-1/P53和CEH-23通过相似的机制调节秀丽线虫ETC缺陷时的寿命。全基因组基因表达谱比较显示，这两个转录因子与AAK-2/AMP激酶(AMPK)信号之间存在新的联系。进一步的功能分析表明，CEP-1/P53和CEH-23在AAK-2/AMPK信号和CRTC-1转录共激活因子的下游发挥作用，促进抗逆性和寿命。由于AAK-2、CEP-1和CEH-23都是高度保守的，我们的发现可能为理解不同生物体对线粒体功能障碍的生物适应性反应提供重要的见解，并将与人类的衰老和线粒体病因学的病理学相关。
A decline in mitochondrial electron transport chain (ETC) function has long been implicated in aging and various diseases. Recently, moderate mitochondrial ETC dysfunction has been found to prolong lifespan in diverse organisms, suggesting a conserved and complex role of mitochondria in longevity determination. Several nuclear transcription factors have been demonstrated to mediate the lifespan extension effect associated with partial impairment of the ETC, suggesting that compensatory transcriptional response to be crucial. In this study, we showed that the transcription factors CEP‐1/p53 and CEH‐23 act through a similar mechanism to modulate longevity in response to defective ETC in Caenorhabditis elegans. Genomewide gene expression profiling comparison revealed a new link between these two transcription factors and AAK‐2/AMP kinase (AMPK) signaling. Further functional analyses suggested that CEP‐1/p53 and CEH‐23 act downstream of AAK‐2/AMPK signaling and CRTC‐1 transcriptional coactivator to promote stress resistance and lifespan. As AAK‐2, CEP‐1, and CEH‐23 are all highly conserved, our findings likely provide important insights for understanding the organismal adaptive response to mitochondrial dysfunction in diverse organisms and will be relevant to aging and pathologies with a mitochondrial etiology in human.
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影响因子：
64.8
作者：
Ishii, N;Fujii, M;Suzuki, K
通讯作者：
Suzuki, K
影响因子：
7.8
作者：
Curtis, R;O'Connor, G;DiStefano, PS
通讯作者：
DiStefano, PS
影响因子：
9.2
作者：
Copeland, Jeffrey M.;Cho, Jaehyoung;Walker, David W.
通讯作者：
Walker, David W.
DOI：
10.1006/bbrc.2001.5627
发表时间：
2001-09-21
影响因子：
3.1
作者：
Imamura, K;Ogura, T;Esumi, H
通讯作者：
Esumi, H
影响因子：
5.3
作者：
Hartman, PS;Ishii, N;Sedensky, MM
通讯作者：
Sedensky, MM