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Novel role of dynamin‐related‐protein 1 in dynamics of ER‐lipid droplets in adipose tissue
Author(s) -
Li Xin,
Yang Li,
Mao Zhengmei,
Pan Xueyang,
Zhao Yueshui,
Gu Xue,
EckelMahan Kristin,
Zuo Zhongyuan,
Tong Qiang,
Hartig Sean M.,
Cheng Xiaodong,
Du Guangwei,
Moore David D.,
Bellen Hugo J.,
Sesaki Hiromi,
Sun Kai
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201903100rr
Subject(s) - lipid droplet , endoplasmic reticulum , adipose tissue , microbiology and biotechnology , mitochondrial fission , dnm1l , organelle , lipid metabolism , dynamin , autophagy , biology , chemistry , mitochondrion , endocrinology , apoptosis , biochemistry , endocytosis , cell
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‐ 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.