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An RDH-Plin2 axis modulates lipid droplet size by antagonizing Bmm lipase

Xuefan Zhao1,2, Wei Wang1, Yan Yao1

  • 1State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Innovation Academy for Seed Design, Chinese Academy of Sciences, Beijing, China.

EMBO Reports
|February 8, 2022
PubMed

Insights

COP9 signalosome (CSN) regulates lipid droplet size by targeting retinol dehydrogenase (RDH). An RDH-Plin2 axis controls lipase levels, crucial for survival during starvation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Lipid droplet size is dynamic, influenced by internal and external factors.
  • The COP9 signalosome (CSN) is a key regulator in various cellular processes.

Purpose of the Study:

  • To investigate the role of CSN in regulating lipid droplet size.
  • To identify CSN targets involved in lipid metabolism.

Main Methods:

  • RNA interference (RNAi) screen in Drosophila.
  • Identification of proteasomal degradation targets.
  • Protein-protein interaction studies.
  • Analysis of lipase localization and levels.

Main Results:

  • Knockdown of CSN subunits enlarged lipid droplets under high-fat conditions.
  • CG2064, a retinol dehydrogenase (RDH) homolog, was identified as a CSN target.
  • The RDH/CG2064-Plin2 axis was found to reduce Brummer (Bmm)/ATGL lipase levels and localization.
  • This axis is essential for larval survival during starvation.

Conclusions:

  • A novel RDH-Plin2 axis regulates lipid droplet size.
  • CSN controls lipid droplet homeostasis through proteasomal degradation of RDH.
  • This pathway is critical for adaptation to nutrient stress.
Keywords:
ATGLRDH/Plin2large lipid droplet

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