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

First Author  Li X Year  2020
Journal  FASEB J Volume  34
Issue  6 Pages  8265-8282
PubMed ID  32294302 Mgi Jnum  J:329423
Mgi Id  MGI:6712972 Doi  10.1096/fj.201903100RR
Citation  Li X, et al. (2020) Novel role of dynamin-related-protein 1 in dynamics of ER-lipid droplets in adipose tissue. FASEB J 34(6):8265-8282
abstractText  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 beta-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-Drp1(flx/flx) ). We found that the LDs in adipose tissues of Adipo-Drp1(flx/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-Drp1(flx/flx) mice.
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