| Autor: |
Xiao, Jian, Luo, Jie, Hu, Ao, Xiao, Ting, Li, Meixin, Kong, Zekai, Jiang, Luyi, Zhou, Zimu, Liao, Yacheng, Xie, Chang, Chu, Beibei, Miao, Honghua, Li, Boliang, Shi, Xiongjie, Song, Bao-Liang |
| Zdroj: |
SCIENCE CHINA Life Sciences; September 2019, Vol. 62 Issue: 9 p1117-1135, 19p |
| Abstrakt: |
Most mammalian cells take up cholesterol from low-density lipoproteins (LDLs) via receptor-mediated endocytosis. After reaching lysosomes, LDL-derived cholesterol continues to transport to downstream organelles including the ER for specific structural and functional needs. Peroxisomes are recently found to receive cholesterol from lysosomes through lysosome-peroxisome membrane contacts. However, whether and how cholesterol is conveyed from peroxisomes to the ER remain unknown. Here, by combining high-resolution microscopic analyses and in vitroreconstitution of highly purified organelles or artificial liposomes, we demonstrate that peroxisomes form membrane contacts with the ER through the interaction between peroxisomal PI(4,5)P2and ER-resident extended synaptotagmin-1, 2 and 3 (E-Syts). Depletion of peroxisomal PI(4,5)P2or E-Syts markedly decreases peroxisome-ER membrane contacts and induces cholesterol accumulation in lysosomes. Furthermore, we show that cholesterol is delivered from 3H-labeled peroxisomes or PI(4,5)P2-containing liposomes to the ER in vitro, and that the presence of peroxisomes augments cholesterol transfer from lysosomes to the ER. Together, our study reveals a new cholesterol transport pathway along the lysosome-peroxisome-ER membrane contacts in the cell. |
| Databáze: |
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