2. Academic Validation
  3. Histone chaperone SSRP1 is required for apoptosis inhibition and mitochondrial function in HCC via transcriptional promotion of TRAP1

Histone chaperone SSRP1 is required for apoptosis inhibition and mitochondrial function in HCC via transcriptional promotion of TRAP1

  • Biochem Cell Biol. 2023 Apr 21. doi: 10.1139/bcb-2023-0006.
Xuyang Chen 1,  Mengxin Li 2,  Ding Wang 3,  Qian Wang 4,  Xiaodong Wei 5,  Xiaorui Liu 6,  Jiaying Yang 7,  Dhan V Kalvakolanu 8,  Baofeng Guo 9,  Ling Zhang 10
Affiliations

Affiliations

  • 1 Jilin University College of Basic Medical Sciences, 623652, Jinlin university, Changchun, Jilin, China; 243236545@qq.com.
  • 2 Jilin University College of Basic Medical Sciences, 623652, Jilin University, Changchun, Jilin, China; 291529584@qq.com.
  • 3 Jilin University College of Basic Medical Sciences, 623652, Jilin University, Changchun, Jilin, China; 937795169@qq.com.
  • 4 Jilin University College of Basic Medical Sciences, 623652, Jilin University, Changchun, Jilin, China; 1546136097@qq.com.
  • 5 Jilin University College of Basic Medical Sciences, 623652, Jilin University, Changchun, Jilin, China; weixiaodong02@qq.com.
  • 6 Jilin University College of Basic Medical Sciences, 623652, Jilin University, Changchun, Jilin, China; 2264991527@qq.com.
  • 7 Jilin University College of Basic Medical Sciences, 623652, Jilin University, Changchun, Jilin, China; 1670309292@qq.com.
  • 8 University of Maryland School of Medicine, 12264, Baltimore, Maryland, United States; trishulam@hotmail.com.
  • 9 Jilin University, 12510, Department of Plastic Surgery, Changchun, China; gbf@jlu.edu.cn.
  • 10 Jilin University College of Basic Medical Sciences, 623652, Jilin University, Changchun, Jilin, China; zhangling3@jlu.edu.cn.
PMID: 37084412 DOI: 10.1139/bcb-2023-0006
Abstract

Epigenetic regulation contributes to human health and disease, especially Cancer, but the mechanisms of many epigenetic regulators remain obscure. Most research is focused on gene regulatory processes, such as mRNA translation and DNA damage repair, rather than the effects on biological functions like mitochondrial activity and Oxidative Phosphorylation. Here, we identified an essential role for the histone chaperone structure-specific recognition protein 1 (SSRP1) in mitochondrial oxidative respiration in hepatocellular carcinoma and found that SSRP1 suppression led to mitochondrial damage and decreased oxidative respiration. Further, we focused on TNF receptor-associated protein 1 (TRAP1), the only member of the heat shock protein 90 (HSP90) family, which directly interacts with selected respiratory complexes and affects their stability and activity. We confirmed that SSRP1 downregulation caused a decrease in TRAP1 expression at both the mRNA and protein levels. A ChIP assay also showed that SSRP1 could deposit in the TRAP1 promoter region, indicating that SSRP1 maintains mitochondrial function and Reactive Oxygen Species levels through TRAP1. Additionally, rescue experiments and animal experiments confirmed the mechanism of SSRP1 and TRAP1 interaction. In summary, we identified a new mechanism that connects mitochondrial respiration and Apoptosis, via SSRP1.

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