A bacteria-derived tetramerized protein ameliorates nonalcoholic steatohepatitis in mice via binding and relocating acetyl-coA carboxylase

被引:0
|
作者
Lin, Yan [1 ]
Yang, Mingkun [7 ]
Huang, Li [3 ]
Yang, Fan [1 ]
Fan, Jiachen [1 ]
Qiang, Yulong [1 ]
Chang, Yuting [1 ]
Zhou, Wenjie [1 ]
Yan, Leilei [1 ]
Xiong, Jie [6 ]
Ping, Jie [4 ]
Chen, Shizhen [5 ]
Men, Dong [2 ]
Li, Feng [1 ,8 ]
机构
[1] Wuhan Univ, TaiKang Med Sch, Sch Basic Med Sci, Dept Med Genet, Wuhan 430071, Peoples R China
[2] Guangzhou Int Bio Isl, Guangzhou Natl Lab, Guangzhou 510005, Guangdong, Peoples R China
[3] Wuhan Univ, Res Ctr Med & Struct Biol, TaiKang Med Sch, Sch Basic Med Sci, Wuhan 430071, Peoples R China
[4] Wuhan Univ, TaiKang Med Sch, Sch Basic Med Sci, Dept Pharmacol, Wuhan 430071, Peoples R China
[5] Chinese Acad Sci, Wuhan Inst Phys & Math, Innovat Acad Precis Measurement Sci & Technol, Natl Ctr Magnet Resonance Wuhan,State Key Lab Magn, Wuhan 430071, Peoples R China
[6] Wuhan Univ, Taikang Med Sch, Sch Basic Med Sci, Dept Immunol, Wuhan 430071, Peoples R China
[7] Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China
[8] Hubei Prov Key Lab Allergy & Immunol, Wuhan 430071, Peoples R China
来源
CELL REPORTS | 2023年 / 42卷 / 11期
基金
中国国家自然科学基金;
关键词
COENZYME-A CARBOXYLASE; PHASE-SEPARATION; INHIBITION; CANCER;
D O I
10.1016/j.celrep.2023.113453
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Increased de novo lipogenesis (DNL) is a major feature of nonalcoholic steatohepatitis (NASH). None of the drugs targeting the catalytic activity of acetyl-CoA carboxylase (ACC), the rate-limiting enzyme in the DNL process, have been approved by the FDA. Whether cytosolic ACC1 can be regulated spatially remains to be explored. Herein, we find that streptavidin (SA), which is a bacterium-derived tetrameric protein, forms cytosolic condensates and efficiently induces a spatial re-localization of ACC1 in liver cells, concomitant with inhibited lipid accumulation. Both SA tetrameric structure and multivalent protein interaction are required for condensate formation. Interestingly, the condensates are further characterized as gel-like membraneless organelle (SAGMO) and significantly restrict the cytosolic dispersion of ACC1 and fatty acid synthase. Notably, AAV-mediated delivery of SA partially blocks mouse liver DNL and ameliorates NASH without eliciting hypertriglyceridemia. In summary, our study shows that insulating lipogenesis-related proteins by SAGMO might be effective for NASH treatment.
引用
收藏
页数:22
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