@article{7b9697d1f9694843b3716875df3965f8,
title = "Novel role of dynamin-related-protein 1 in dynamics of ER-lipid droplets in adipose tissue",
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.",
keywords = "ER retention, LD budding, LD morphology, energy expenditure, lipolysis",
author = "Xin Li and Li Yang and Zhengmei Mao and Xueyang Pan and Yueshui Zhao and Xue Gu and Kristin Eckel-Mahan and Zhongyuan Zuo and Qiang Tong and Hartig, {Sean M.} and Xiaodong Cheng and Guangwei Du and Moore, {David D.} and Bellen, {Hugo J.} and Hiromi Sesaki and Kai Sun",
note = "Funding Information: We thank our colleagues, particularly members in Dr Kolonin's group at Center of Metabolic and Degenerative Diseases for technical support. We further thank Dr Hongyuan Yang at UNSW and Dr Pingsheng Liu at Chinese Academy of Sciences for the informative discussions and thoughtful suggestions. The authors would like to thank AFM SEM core in Houston Methodist Research Institute and High Resolution Electron Microscopy Facility at UT MD Anderson Cancer Center for the EM study. This study was supported by National Institute of Health (NIH) grant R01DK109001 (to KS), NIGMS grant R35GM122536 (to XC), USDA CRIS 3092-5-001-059, and AHA grant 18TPA34170539 (to QT), NIH grant GM123266 (to HS), NIH grant R01DK114356, and American Diabetes Association grant #1-18-IBS-105 (to SH), AHA grant 19TPA34910051 (to G.D), NIH grant AR075830 (to G.D) as well as NIH grant R01DK114037 (to K.L. Eckel-Mahan). Funding Information: We thank our colleagues, particularly members in Dr Kolonin's group at Center of Metabolic and Degenerative Diseases for technical support. We further thank Dr Hongyuan Yang at UNSW and Dr Pingsheng Liu at Chinese Academy of Sciences for the informative discussions and thoughtful suggestions. The authors would like to thank AFM SEM core in Houston Methodist Research Institute and High Resolution Electron Microscopy Facility at UT MD Anderson Cancer Center for the EM study. This study was supported by National Institute of Health (NIH) grant R01DK109001 (to KS), NIGMS grant R35GM122536 (to XC), USDA CRIS 3092‐5‐001‐059, and AHA grant 18TPA34170539 (to QT), NIH grant GM123266 (to HS), NIH grant R01DK114356, and American Diabetes Association grant #1‐18‐IBS‐105 (to SH), AHA grant 19TPA34910051 (to G.D), NIH grant AR075830 (to G.D) as well as NIH grant R01DK114037 (to K.L. Eckel‐Mahan). Publisher Copyright: {\textcopyright} 2020 Federation of American Societies for Experimental Biology Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2020",
month = jun,
day = "1",
doi = "10.1096/fj.201903100RR",
language = "English (US)",
volume = "34",
pages = "8265--8282",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "6",
}