期刊
DEVELOPMENT
卷 145, 期 4, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.161893
关键词
Autophagy; Lipid droplet; Oocyte; Embryo; Mouse
资金
- Japan Society for the Promotion of Science (KAKENHI Program) [16H06167, 16H01194, 25111001, 15H05637]
- Japan Agency for Medical Research and Development [16gk0110015h0001]
- Naito Foundation
- Senri Life Science Foundation
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [16H06167, 16H01194, 25111001, 25111005, 15H05637, 16H05042] Funding Source: KAKEN
Although autophagy is classically viewed as a non-selective degradation system, recent studies have revealed that various forms of selective autophagy also play crucial physiological roles. However, the induction of selective autophagy is not well understood. In this study, we established a forced selective autophagy system using a fusion of an autophagy adaptor and a substrate-binding protein. In both mammalian cells and fertilized mouse embryos, efficient forced lipophagy was induced by expression of a fusion of p62 (Sqstm1) and a lipid droplet (LD)-binding domain. In mouse embryos, induction of forced lipophagy caused a reduction in LD size and number, and decreased the triglyceride level throughout embryonic development, resulting in developmental retardation. Furthermore, lipophagy-induced embryos could eliminate excess LDs and were tolerant of lipotoxicity. Thus, by inducing forced lipophagy, expression of the p62 fusion protein generated LD-depleted cells, revealing an unexpected role of LD during preimplantation development.
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