Acta Biochimica et Biophysica Sinica (Apr 2023)

Homocysteine accelerates hepatocyte autophagy by upregulating TFEB via DNMT3b-mediated DNA hypomethylation

  • Yang Anning,
  • Zeng Wen,
  • Zhang Hongwen,
  • Hao Yinju,
  • Wang Qingqing,
  • Sun Yue,
  • Quan Shangkun,
  • Ding Ning,
  • Yang Xiaoling,
  • Sun Jianmin,
  • Zhang Huiping,
  • Liu Bin,
  • Jiao Yun,
  • Wu Kai,
  • Jiang Yideng

DOI
https://doi.org/10.3724/abbs.2023060
Journal volume & issue
Vol. 55
pp. 1184 – 1192

Abstract

Read online

Autophagy plays a critical role in the physiology and pathophysiology of hepatocytes. High level of homocysteine (Hcy) promotes autophagy in hepatocytes, but the underlying mechanism is still unknown. Here, we investigate the relationship between Hcy-induced autophagy level and the expression of nuclear transcription factor EB (TFEB). The results show that Hcy-induced autophagy level is mediated by upregulation of TFEB. Silencing of TFEB decreases the level of autophagy-related protein LC3BII/I and increases p62 expression level in hepatocytes after exposure to Hcy. Moreover, the effect of Hcy on the expression of TFEB is regulated by hypomethylation of the TFEB promoter catalyzed by DNA methyltransferase 3b (DNMT3b). In summary, this study shows that Hcy can activate autophagy by inhibiting DNMT3b-mediated DNA methylation and upregulating TFEB expression. These findings provide another new mechanism for Hcy-induced autophagy in hepatocytes.

Keywords