2. Academic Validation
  3. P300/HDAC1 regulates the acetylation/deacetylation and autophagic activities of LC3/Atg8-PE ubiquitin-like system

P300/HDAC1 regulates the acetylation/deacetylation and autophagic activities of LC3/Atg8-PE ubiquitin-like system

  • Cell Death Discov. 2021 May 31;7(1):128. doi: 10.1038/s41420-021-00513-0.
Wenmei Wu  # 1 2,  Kang Li  # 3,  Sanyou Guo 1 2,  Jing Xu 1 2,  Qiuqin Ma 1 2,  Shuyan Li 1 2,  Xianying Xu 1 2,  Zhijun Huang 1 2,  Yangjin Zhong 1 2,  Gianluca Tettamanti 4 5,  Yang Cao 6 7,  Sheng Li 8,  Ling Tian 9 10
Affiliations

Affiliations

  • 1 Guangdong Laboratory for Lingnan Modern Agriculture/Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, 510642, Guangzhou, China.
  • 2 Guangdong Provincial Sericulture and Mulberry Engineering Research Center, College of Animal Science, South China Agricultural University, 510642, Guangzhou, China.
  • 3 Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University, 510631, Guangzhou, China.
  • 4 Department of Biotechnology and Life Sciences, University of Insubria, 21100, Varese, Italy.
  • 5 BAT Center-Interuniversity Center for Studies on Bioinspired Agro-Environmental Technology, University of Napoli Federico II, 80138, Napoli, Italy.
  • 6 State Key Laboratory of Silkworm Genome Biology, Southwest University, 400716, Chongqing, China. caoyang@scau.edu.cn.
  • 7 Biological Science Research Center/Chongqing Engineering and Technology Research Center for Novel Silk Materials, Southwest University, 400716, Chongqing, China. caoyang@scau.edu.cn.
  • 8 Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University, 510631, Guangzhou, China. lisheng@scnu.edu.cn.
  • 9 Guangdong Laboratory for Lingnan Modern Agriculture/Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, 510642, Guangzhou, China. tianling@scau.edu.cn.
  • 10 Guangdong Provincial Sericulture and Mulberry Engineering Research Center, College of Animal Science, South China Agricultural University, 510642, Guangzhou, China. tianling@scau.edu.cn.
  • # Contributed equally.
PMID: 34059632 DOI: 10.1038/s41420-021-00513-0
Abstract

Protein acetylation plays potential roles in regulating Autophagy occurrence. However, it varies greatly between yeast and mammals, and has not been thoroughly investigated in other organisms. Here, we reported that the components of BmAtg8-PE ubiquitin-like system (BmAtg3, BmAtg4, BmAtg7, and BmAtg8) in Bombyx mori were localized in the nucleus under nutrient-rich conditions, whereas they were exported to the cytoplasm upon Autophagy induction. RNAi of BmP300 and inhibition of BmP300 activity resulted in nucleo-cytoplasmic translocation of BmAtg3 and BmAtg8, as well as premature induction of Autophagy in the absence of stimulus. Conversely, RNAi of BmHDAC1 and inhibition of class I/II HADCs activities led to the nuclear accumulation of BmAtg3 and BmAtg8. In addition, acetylation sites in Atg proteins of BmAtg8-PE ubiquitin-like system were identified by mass spectrometry, and acetylation-site mutations caused nucleo-cytoplasmic translocation of BmAtg3, BmAtg4, and BmAtg8 along with Autophagy promotion. Similarly, the subcellular localization of human ATG4b is determined by acetylation modification. In general, BmP300-mediated acetylation sequesters the components of BmAtg8-PE ubiquitin-like system in the nucleus, thus leading to the Autophagy inhibition. Oppositely, BmHDAC1-mediated deacetylation leads to the nucleo-cytoplasmic translocation of the components of BmAtg8-PE ubiquitin-like system and promotes Autophagy. This process is evolutionarily conserved between insects and mammals.

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