Loss of Splicing Factor SRSF3 Impairs Lipophagy Through Ubiquitination and Degradation of Syntaxin17 in Hepatocytes

作者全名："Li, Yun; Wang, Tao; Liao, Qiumin; Luo, Xiaoting; Wang, Xing; Zeng, Shu; You, Mengyue; Chen, Yaxi; Ruan, Xiong Z."

作者地址："[Li, Yun; Wang, Tao; Liao, Qiumin; Luo, Xiaoting; Wang, Xing; Zeng, Shu; You, Mengyue; Chen, Yaxi; Ruan, Xiong Z.] Chongqing Med Univ, Affiliated Hosp 2, Minist Educ, Ctr Lipid Res, Chongqing, Peoples R China; [Li, Yun; Wang, Tao; Liao, Qiumin; Luo, Xiaoting; Wang, Xing; Zeng, Shu; You, Mengyue; Chen, Yaxi; Ruan, Xiong Z.] Chongqing Med Univ, Affiliated Hosp 2, Minist Educ, Key Lab Mol Biol Infect Dis, Chongqing, Peoples R China; [Ruan, Xiong Z.] UCL, Ctr Nephrol, Med Sch, John Moorhead Res Lab, Royal Free Campus, London, England"

通信作者："Chen, YX; Ruan, XZ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Minist Educ, Ctr Lipid Res, Chongqing, Peoples R China.; Chen, YX; Ruan, XZ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Minist Educ, Key Lab Mol Biol Infect Dis, Chongqing, Peoples R China.; Ruan, XZ (通讯作者)，UCL, Ctr Nephrol, Med Sch, John Moorhead Res Lab, Royal Free Campus, London, England."

来源：JOURNAL OF LIPID RESEARCH

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000955247000001

JCR分区：Q1

影响因子：5

年份：2023

卷号：64

期号：3

开始页：　

结束页：　

文献类型：Article

关键词：lipid droplets; liver; triglyceride; obesity; lipid; oxidation; NAFLD; autophagic flux; proteasome; SNARE protein; E3 ligase

摘要："Lipid accumulation in hepatocytes is the distinctive characteristic of nonalcoholic fatty liver disease. Serine/arginine-rich splicing factor 3 (SRSF3) is highly expressed in the liver and expression de-creases in high-fat conditions. However, the role of SRSF3 in hepatic lipid metabolism needs to be clari-fied. Here, we showed that loss of SRSF3 was associ-ated with lipid accumulation. We determined that SRSF3 regulated lipophagy, the process of selective degradation of lipid droplets by autophagy. Mecha-nistically, loss of SRSF3 impaired the fusion of the autophagosome and lysosome by promoting the pro-teasomal degradation of syntaxin 17 (STX17), a key autophagosomal SNARE protein. We found that ubiquitination of STX17 was increased and upregu-lation of seven in absentia homolog 1 was responsible for the increased posttranslational modification of STX17. Taken together, our data primarily demon-strate that loss of SRSF3 weakens the clearance of fatty acids by impairing lipophagy in the progression of nonalcoholic fatty liver disease, indicating a novel potential therapeutic target for fatty liver disease treatment."

基金机构："National Natural Science Foundation of China [82000539, 32030054]; Chongqing Postdoctoral Science Fund Project [cstc2020jcyj-bshX0080]; China Postdoctoral Science Foundation [2020M673162]; Special Grant for Chongqing Postdoctoral Researcher Research Project [2021XM1014]; Chongqing Research Program of Basic Research and Frontier Technology [cstc2020jcyj-zdxmX0007]; Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University; 111 Project [D20028]"

基金资助正文："This work was supported by the National Natural Science Foundation of China [grant number 82000539, 32030054] ; Chongqing Postdoctoral Science Fund Project (grant number cstc2020jcyj-bshX0080) , China Postdoctoral Science Foundation Grant (grant number 2020M673162) , and Special Grant for Chongqing Postdoctoral Researcher Research Project (grant number 2021XM1014) . The current research was also partially supported by the Chongqing Research Program of Basic Research and Frontier Technology (grant number cstc2020jcyj-zdxmX0007) and the Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University; the 111 Project (grant number D20028) ."