Histone deacetylase HDA-1 modulates mitochondrial stress response and longevity
Histone deacetylase HDA-1 modulates mitochondrial stress response and longevity
复制标题
组蛋白脱乙酰酶 HDA-1 调节线粒体应激反应和寿命
DOI：
10.1038/s41467-020-18501-w
复制
发表时间：
2020-09-15
影响因子：
16.6
通讯作者：
Liu, Ying
中科院分区：
文献类型：
--
作者：
Shao, Li-Wa;Peng, Qi;Liu, Ying
检测、响应和适应线粒体应激的能力确保了生物体的发育和生存。秀丽隐杆线虫通过激活线粒体未折叠蛋白反应（UPRmt）来缓冲线粒体折叠环境，重塑代谢状态，促进先天免疫和寿命延长，从而应对线粒体应激。这里我们展示了HDA-1， c。哺乳动物组蛋白去乙酰化酶（HDAC）是线粒体应激介导的UPRmt激活所必需的。HDA-1与基因组组织者ve -1相互作用并协调，诱导广泛的UPRmt、先天免疫反应和代谢重编程基因的转录。在恒河猴和人类组织中，HDAC1/2转录水平与UPRmtgenes的表达相关。敲除或药理抑制HDAC1/2会破坏哺乳动物细胞中uprmt2和线粒体网络的激活。我们的研究结果强调了HDAC1/2在调节线粒体稳态和调节寿命方面的进化保守机制。
The ability to detect, respond and adapt to mitochondrial stress ensures the development and survival of organisms.Caenorhabditis elegansresponds to mitochondrial stress by activating the mitochondrial unfolded protein response (UPRmt) to buffer the mitochondrial folding environment, rewire the metabolic state, and promote innate immunity and lifespan extension. Here we show that HDA-1, theC. elegansortholog of mammalian histone deacetylase (HDAC) is required for mitochondrial stress-mediated activation of UPRmt. HDA-1 interacts and coordinates with the genome organizer DVE-1 to induce the transcription of a broad spectrum of UPRmt, innate immune response and metabolic reprogramming genes. In rhesus monkey and human tissues, HDAC1/2 transcript levels correlate with the expression of UPRmtgenes. Knocking down or pharmacological inhibition of HDAC1/2 disrupts the activation of the UPRmtand the mitochondrial network in mammalian cells. Our results underscore an evolutionarily conserved mechanism of HDAC1/2 in modulating mitochondrial homeostasis and regulating longevity.