Forced lipophagy reveals that lipid droplets are required for early embryonic development in mouse

Takayuki Tatsumi, Kaori Takayama, Shunsuke Ishii, Atsushi Yamamoto, Taichi Hara, Naojiro Minami, Naoyuki Miyasaka, Toshiro Kubota, Akira Matsuura, Eisuke Itakura, Satoshi Tsukamoto

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalDevelopment (Cambridge, England)
Volume145
Issue number4
DOIs
Publication statusPublished - 2018 Feb 23
Externally publishedYes

Keywords

  • Autophagy
  • Embryo
  • Lipid droplet
  • Mouse
  • Oocyte

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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    Tatsumi, T., Takayama, K., Ishii, S., Yamamoto, A., Hara, T., Minami, N., Miyasaka, N., Kubota, T., Matsuura, A., Itakura, E., & Tsukamoto, S. (2018). Forced lipophagy reveals that lipid droplets are required for early embryonic development in mouse. Development (Cambridge, England), 145(4). https://doi.org/10.1242/dev.161893