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Bile acids-mediated intracellular cholesterol transport promotes intestinal cholesterol absorption and NPC1L1 recycling

Author

Listed:
  • Jian Xiao

    (Wuhan University)

  • Le-Wei Dong

    (Wuhan University)

  • Shuai Liu

    (Wuhan University
    First Affiliated Hospital of Xinjiang Medical University)

  • Fan-Hua Meng

    (Wuhan University
    First Affiliated Hospital of Xinjiang Medical University
    Affiliated Hospital of Jining Medical University)

  • Chang Xie

    (Wuhan University)

  • Xiao-Yi Lu

    (Wuhan University)

  • Weiping J. Zhang

    (Naval Medical University)

  • Jie Luo

    (Wuhan University)

  • Bao-Liang Song

    (Wuhan University)

Abstract

Niemann-Pick C1-like 1 (NPC1L1) is essential for intestinal cholesterol absorption. Together with the cholesterol-rich and Flotillin-positive membrane microdomain, NPC1L1 is internalized via clathrin-mediated endocytosis and transported to endocytic recycling compartment (ERC). When ERC cholesterol level decreases, NPC1L1 interacts with LIMA1 and moves back to plasma membrane. However, how cholesterol leaves ERC is unknown. Here, we find that, in male mice, intracellular bile acids facilitate cholesterol transport to other organelles, such as endoplasmic reticulum, in a non-micellar fashion. When cholesterol level in ERC is decreased by bile acids, the NPC1L1 carboxyl terminus that previously interacts with the cholesterol-rich membranes via the A1272LAL residues dissociates from membrane, exposing the Q1277KR motif for LIMA1 recruitment. Then NPC1L1 moves back to plasma membrane. This study demonstrates an intracellular cholesterol transport function of bile acids and explains how the substantial amount of cholesterol in NPC1L1-positive compartments is unloaded in enterocytes during cholesterol absorption.

Suggested Citation

  • Jian Xiao & Le-Wei Dong & Shuai Liu & Fan-Hua Meng & Chang Xie & Xiao-Yi Lu & Weiping J. Zhang & Jie Luo & Bao-Liang Song, 2023. "Bile acids-mediated intracellular cholesterol transport promotes intestinal cholesterol absorption and NPC1L1 recycling," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42179-5
    DOI: 10.1038/s41467-023-42179-5
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    References listed on IDEAS

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    1. Jian-Wei Hao & Juan Wang & Huiling Guo & Yin-Yue Zhao & Hui-Hui Sun & Yi-Fan Li & Xiao-Ying Lai & Ning Zhao & Xu Wang & Changchuan Xie & Lixin Hong & Xi Huang & Hong-Rui Wang & Cheng-Bin Li & Bin Lian, 2020. "CD36 facilitates fatty acid uptake by dynamic palmitoylation-regulated endocytosis," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
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