Journal Article

Histone deacetylase HDA-1 modulates mitochondrial stress response and longevity

Peng, Qi, Li, Yumei, Liu, Ying, Li, Chuan-Yun, Dong, Mingyue, Shao, Li-Wa, Gao, Kaiyu, Li, Yi

2020

Overview

The ability to detect, respond and adapt to mitochondrial stress ensures the development and survival of organisms. Caenorhabditis elegans responds to mitochondrial stress by activating the mitochondrial unfolded protein response (UPR mt ) to buffer the mitochondrial folding environment, rewire the metabolic state, and promote innate immunity and lifespan extension. Here we show that HDA-1, the C. elegans ortholog of mammalian histone deacetylase (HDAC) is required for mitochondrial stress-mediated activation of UPR mt . HDA-1 interacts and coordinates with the genome organizer DVE-1 to induce the transcription of a broad spectrum of UPR mt , innate immune response and metabolic reprogramming genes. In rhesus monkey and human tissues, HDAC1/2 transcript levels correlate with the expression of UPR mt genes. Knocking down or pharmacological inhibition of HDAC1/2 disrupts the activation of the UPR mt and the mitochondrial network in mammalian cells. Our results underscore an evolutionarily conserved mechanism of HDAC1/2 in modulating mitochondrial homeostasis and regulating longevity. Caenorhabditis elegans responds to mitochondrial stress by activating the mitochondrial unfolded protein response (UPR mt ). Here the authors show that HDA-1, the C. elegans ortholog of mammalian histone deacetylase (HDAC), coordinates with the genome organizer DVE-1 to activate UPR mt and modulate mitochondrial homeostasis.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 14/35 / 38 / 38/15 / 38/91 / 631/337 / 631/80 / 64/11 / Activation / Animals / Caenorhabditis elegans / Caenorhabditis elegans - enzymology / Caenorhabditis elegans - genetics / Caenorhabditis elegans - growth & development / Caenorhabditis elegans Proteins - genetics / Caenorhabditis elegans Proteins - metabolism / Gene expression / Genes / Genomes / Histone deacetylase / Histone Deacetylase 1 - genetics / Histone Deacetylase 1 - metabolism / Histone Deacetylase 2 - genetics / Histone Deacetylase 2 - metabolism / Histone Deacetylases - genetics / Histone Deacetylases - metabolism / Histones / Homeostasis / Human tissues / Humanities and Social Sciences / Immune response / Immune system / Innate immunity / Life span / Longevity / Macaca mulatta / Mammalian cells / Mammals / Metabolism / Mitochondria / Mitochondria - enzymology / multidisciplinary / Nematodes / Protein folding / Proteins / Science / Science (multidisciplinary) / Stress, Physiological / Transcription / Unfolded Protein Response / Worms