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Molecular probes for tracking lipid droplet membrane dynamics

Author

Listed:
  • Lingxiu Kong

    (Shandong First Medical University & Shandong Academy of Medical Sciences)

  • Qingjie Bai

    (Shandong First Medical University & Shandong Academy of Medical Sciences
    Shandong First Medical University & Shandong Academy of Medical Sciences)

  • Cuicui Li

    (National University of Singapore
    National University of Singapore
    National University of Singapore
    Helios)

  • Qiqin Wang

    (Shandong First Medical University & Shandong Academy of Medical Sciences
    Jinan University)

  • Yanfeng Wang

    (Shandong First Medical University & Shandong Academy of Medical Sciences)

  • Xintian Shao

    (Shandong First Medical University & Shandong Academy of Medical Sciences
    Shandong First Medical University & Shandong Academy of Medical Sciences
    Shandong First Medical University & Shandong Academy of Medical Sciences)

  • Yongchun Wei

    (Shandong First Medical University & Shandong Academy of Medical Sciences)

  • Jiarao Sun

    (Shandong First Medical University & Shandong Academy of Medical Sciences)

  • Zhenjie Yu

    (Shandong First Medical University & Shandong Academy of Medical Sciences)

  • Junling Yin

    (Shandong First Medical University & Shandong Academy of Medical Sciences)

  • Bin Shi

    (Shandong First Medical University & Shandong Academy of Medical Sciences
    Shandong First Medical University & Shandong Academy of Medical Sciences)

  • Hongbao Fang

    (Nanjing Normal University)

  • Xiaoyuan Chen

    (National University of Singapore
    National University of Singapore
    National University of Singapore
    Helios)

  • Qixin Chen

    (Shandong First Medical University & Shandong Academy of Medical Sciences
    Shandong First Medical University & Shandong Academy of Medical Sciences
    National University of Singapore
    National University of Singapore)

Abstract

Lipid droplets (LDs) feature a unique monolayer lipid membrane that has not been extensively studied due to the lack of suitable molecular probes that are able to distinguish this membrane from the LD lipid core. In this work, we present a three-pronged molecular probe design strategy that combines lipophilicity-based organelle targeting with microenvironment-dependent activation and design an LD membrane labeling pro-probe called LDM. Upon activation by the HClO/ClO− microenvironment that surrounds LDs, LDM pro-probe releases LDM-OH probe that binds to LD membrane proteins thus enabling visualization of the ring-like LD membrane. By utilizing LDM, we identify the dynamic mechanism of LD membrane contacts and their protein accumulation parameters. Taken together, LDM represents the first molecular probe for imaging LD membranes in live cells to the best of our knowledge, and represents an attractive tool for further investigations into the specific regulatory mechanisms with LD-related metabolism diseases and drug screening.

Suggested Citation

  • Lingxiu Kong & Qingjie Bai & Cuicui Li & Qiqin Wang & Yanfeng Wang & Xintian Shao & Yongchun Wei & Jiarao Sun & Zhenjie Yu & Junling Yin & Bin Shi & Hongbao Fang & Xiaoyuan Chen & Qixin Chen, 2024. "Molecular probes for tracking lipid droplet membrane dynamics," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53667-7
    DOI: 10.1038/s41467-024-53667-7
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    References listed on IDEAS

    as
    1. Qixin Chen & Hongbao Fang & Xintian Shao & Zhiqi Tian & Shanshan Geng & Yuming Zhang & Huaxun Fan & Pan Xiang & Jie Zhang & Xiaohe Tian & Kai Zhang & Weijiang He & Zijian Guo & Jiajie Diao, 2020. "A dual-labeling probe to track functional mitochondria–lysosome interactions in live cells," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    2. Zixuan Zhou & Jianping Liu & Tao Fu & Ping Wu & Chao Peng & Xinyu Gong & Yingli Wang & Mingfang Zhang & Ying Li & Yaru Wang & Xiaolong Xu & Miao Li & Lifeng Pan, 2021. "Phosphorylation regulates the binding of autophagy receptors to FIP200 Claw domain for selective autophagy initiation," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    3. Noble Kumar Talari & Ushodaya Mattam & Niroj Kumar Meher & Arun Kumar Paripati & Kalyankar Mahadev & Thanuja Krishnamoorthy & Naresh Babu V. Sepuri, 2023. "Lipid-droplet associated mitochondria promote fatty-acid oxidation through a distinct bioenergetic pattern in male Wistar rats," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Jingru Wang & Na Fang & Juan Xiong & Yuanjiao Du & Yue Cao & Wei-Ke Ji, 2021. "An ESCRT-dependent step in fatty acid transfer from lipid droplets to mitochondria through VPS13D−TSG101 interactions," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    5. Mergim Ramosaj & Sofia Madsen & Vanille Maillard & Valentina Scandella & Daniel Sudria-Lopez & Naoya Yuizumi & Ludovic Telley & Marlen Knobloch, 2021. "Lipid droplet availability affects neural stem/progenitor cell metabolism and proliferation," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    6. Karl Zhanghao & Wenhui Liu & Meiqi Li & Zihan Wu & Xiao Wang & Xingye Chen & Chunyan Shan & Haoqian Wang & Xiaowei Chen & Qionghai Dai & Peng Xi & Dayong Jin, 2020. "High-dimensional super-resolution imaging reveals heterogeneity and dynamics of subcellular lipid membranes," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
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