CIDE proteins and their regulatory mechanisms in lipid droplet fusion and growth

Li Xu1, Lizhen Li1, Lingzhi Wu2

  • 1State Key Laboratory of Membrane Biology and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.

FEBS Letters
|February 14, 2024
PubMed

Insights

Cell death-inducing DFF45-like effector (CIDE) proteins regulate lipid homeostasis by controlling lipid droplet fusion. This review details their physiological roles and a proposed four-step mechanism for lipid droplet fusion.

Area of Science:

  • Lipid Metabolism
  • Cell Biology
  • Molecular Biology

Background:

  • Cell death-inducing DFF45-like effector (CIDE) proteins are crucial regulators of lipid homeostasis.
  • These proteins, including Cidea, Cideb, and Cidec/Fsp27, influence lipid storage, lipolysis, and secretion.
  • Dysregulation of CIDE proteins is implicated in metabolic disorders.

Purpose of the Study:

  • To review the physiological roles of CIDE proteins in lipid homeostasis.
  • To elucidate the mechanism of CIDE-mediated lipid droplet (LD) fusion.
  • To identify CIDE-interacting proteins involved in LD fusion regulation.

Main Methods:

  • Analysis of knockout mouse models with CIDE protein deficiencies.
  • Examination of human patients with mutations in CIDE genes.
  • In vitro studies investigating CIDE protein localization and function on lipid droplets.

Main Results:

  • CIDE proteins primarily localize to lipid droplets, controlling their fusion and growth.
  • A four-step model for LD fusion is proposed, involving CIDE recruitment, condensate formation, lipid transfer, and fusion completion.
  • Key CIDE-interacting proteins have been identified as regulators of LD fusion.

Conclusions:

  • CIDE proteins play a central role in regulating lipid droplet dynamics and overall lipid homeostasis.
  • The proposed four-step mechanism provides a framework for understanding CIDE-mediated LD fusion.
  • Further research into CIDE-interacting proteins may reveal novel therapeutic targets for metabolic diseases.

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