School of Biotechnology, Tianjin University of Science and Technology, Key Lab of Industrial Fermentation Microbiology of the Ministry of Education, State Key Laboratory of Food Nutrition and Safety, Tianjin 300457, China.
Biochem Cell Biol. 2021 Oct;99(5):519-526. doi: 10.1139/bcb-2020-0570. Epub 2021 Feb 9.
Autophagy plays a key role in the metabolism of macromolecules via the degradative abilities of the lysosome. Transcription factor EB (TFEB) regulates autophagosome biogenesis and lysosome function, and promoting TFEB activity has emerged as a potential strategy for the treatment of metabolic disorders. Herein, we report that cetrimonium bromide (CTAB; a quaternary ammonium compound) promotes autophagy and lysosomal biogenesis by inducing the nuclear translocation of TFEB in hepatic cells. Knockdown of TFEB mediated by short hairpin RNA inhibits CTAB-induced autophagy and lysosomal biogenesis. Mechanistically, CTAB treatment inhibits the Akt-mTORC1 signaling pathway. Moreover, CTAB treatment significantly increases lipid metabolism in both palmitate- and oleate-treated HepG2 cells, and this increase was attenuated by knockdown of TFEB. Collectively, our results indicate that CTAB activates the autophagosome-lysosome pathway via inducing the nuclear translocation of TFEB by inhibiting the mTORC1 signaling pathway. These results add to the collective understanding of TFEB function and provide new insights into CTAB-mediated lipid metabolism.
自噬通过溶酶体的降解能力在大分子代谢中发挥关键作用。转录因子 EB（TFEB）调节自噬体生物发生和溶酶体功能，促进 TFEB 活性已成为治疗代谢紊乱的一种潜在策略。在此，我们报告溴化十六烷基三甲铵（CTAB；一种季铵化合物）通过诱导 TFEB 在肝细胞中的核易位来促进自噬和溶酶体生物发生。短发夹 RNA 介导的 TFEB 敲低抑制 CTAB 诱导的自噬和溶酶体生物发生。在机制上，CTAB 处理抑制 Akt-mTORC1 信号通路。此外，CTAB 处理显著增加了棕榈酸和油酸处理的 HepG2 细胞中的脂质代谢，而 TFEB 敲低则减弱了这种增加。总之，我们的结果表明，CTAB 通过抑制 mTORC1 信号通路诱导 TFEB 的核易位来激活自噬体-溶酶体途径。这些结果增加了对 TFEB 功能的综合理解，并为 CTAB 介导的脂质代谢提供了新的见解。
