Novel role of dynamin-related-protein 1 in dynamics of ER-lipid droplets in adipose tissue

Xin Li, Li Yang, Zhengmei Mao, Xueyang Pan, Yueshui Zhao, Xue Gu, Kristin Eckel-Mahan, Zhongyuan Zuo, Qiang Tong, Sean M. Hartig, Xiaodong Cheng, Guangwei Du, David D. Moore, Hugo J. Bellen, Hiromi Sesaki, Kai Sun

Research output: Contribution to journalArticlepeer-review

Abstract

Dynamin-Related-Protein 1 (DRP1) critically regulates mitochondrial and peroxisomal fission in multicellular organisms. However, the impact of DRP1 on other organelles, especially its direct influence on ER functions remains largely unclear. Here, we report that DRP1 translocates to endoplasmic reticulum (ER) in response to β-adrenergic stimulation. To further investigate the function of DRP1 on ER-lipid droplet (LD) dynamics and the metabolic subsequences, we generated an adipose tissue-specific DRP1 knockout model (Adipo-Drp1flx/flx). We found that the LDs in adipose tissues of Adipo-Drp1flx/flx mice exhibited more unilocular morphology with larger sizes, and formed less multilocular structures upon cold exposure. Mechanistically, we discovered that abnormal LD morphology occurs because newly generated micro-LDs fail to dissociate from the ER due to DRP1 ablation. Conversely, the ER retention of LDs can be rescued by the overexpressed DRP1 in the adipocytes. The alteration of LD dynamics, combined with abnormal mitochondrial and autophagy functions in adipose tissue, ultimately lead to abnormalities in lipid metabolism in Adipo-Drp1flx/flx mice.

Original languageEnglish (US)
Pages (from-to)8265-8282
Number of pages18
JournalFASEB Journal
Volume34
Issue number6
DOIs
StatePublished - Jun 1 2020

Keywords

  • ER retention
  • LD budding
  • LD morphology
  • energy expenditure
  • lipolysis

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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