AI Article Synopsis
- Dynamin-Related-Protein 1 (DRP1) plays a crucial role in regulating the fission of mitochondria and peroxisomes, and its effects on the endoplasmic reticulum (ER) remain underexplored.
- Researchers developed an adipose tissue-specific DRP1 knockout model to examine how DRP1 affects lipid droplet (LD) dynamics and metabolism.
- Findings showed that in the absence of DRP1, lipid droplets in adipose tissue displayed abnormal sizes and shapes, disrupting lipid metabolism and mitochondrial function, which could be corrected by overexpressing DRP1.
Article 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-Drp1 ). We found that the LDs in adipose tissues of Adipo-Drp1 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 mice.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336545 | PMC |
| http://dx.doi.org/10.1096/fj.201903100RR | DOI Listing |
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