脂肪顕微鏡法:細胞内脂質の可視化(Fat microscopy: Imaging lipids in cells)

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2025-09-01 マックス・プランク研究所

ドレスデンのMPI‑CBG研究チームは、新たな蛍光顕微鏡技術「Fat microscopy」を開発し、細胞内で脂質(リピッド)分子を可視化することに成功した。この手法では、脂質をほぼ天然型と同等に保持した二機能性(UV活性化、蛍光マーキング可能)リポッド類似体を合成し、細胞膜に取り込ませる。UV照射により脂質が近傍のタンパク質と結合・固定され、通常の蛍光顕微鏡で移動を追跡可能とする。画像解析にはAI支援の自動セグメンテーションと数理モデルを活用し、膜コンパートメント間の脂質輸送速度や経路を定量的に再現。85〜95%の脂質が、輸送小胞(ベシクル)ではなくキャリアタンパク質による非小胞性輸送で行われており、速度も10倍速いことを明らかにした。この技術は脂質代謝や神経変性疾患など、脂質関連病態のメカニズム解明や治療標的探索に貢献すると期待される。

脂肪顕微鏡法:細胞内脂質の可視化(Fat microscopy: Imaging lipids in cells)
A microscope picture of human bone cells (U2OS) showing the localization of a lipid (phosphatidylethanolamine). The lipid is visible in orange, the cell membrane in purple, and endosomes in white.
© Kristin Böhlig and Juan Iglesias-Artola / Nature (2025) / MPI-CBG

<関連情報>

哺乳類細胞における脂質輸送の定量的イメージング Quantitative imaging of lipid transport in mammalian cells

Juan M. Iglesias-Artola,Kristin Böhlig,Kai Schuhmann,Katelyn C. Cook,H. Mathilda Lennartz,Milena Schuhmacher,Pavel Barahtjan,Cristina Jiménez López,Radek Šachl,Vannuruswamy Garikapati,Karina Pombo-Garcia,Annett Lohmann,Petra Riegerová,Martin Hof,Björn Drobot,Andrej Shevchenko,Alf Honigmann & André Nadler
Nature  Published:20 August 2025
DOI:https://doi.org/10.1038/s41586-025-09432-x

Abstract

Eukaryotic cells produce over 1,000 different lipid species that tune organelle membrane properties, control signalling and store energy1,2. How lipid species are selectively sorted between organelles to maintain specific membrane identities is largely unclear, owing to the difficulty of imaging lipid transport in cells3. Here we measured the retrograde transport and metabolism of individual lipid species in mammalian cells using time-resolved fluorescence imaging of bifunctional lipid probes in combination with ultra-high-resolution mass spectrometry and mathematical modelling. Quantification of lipid flux between organelles revealed that directional, non-vesicular lipid transport is responsible for fast, species-selective lipid sorting, in contrast to the slow, unspecific vesicular membrane trafficking. Using genetic perturbations, we found that coupling between energy-dependent lipid flipping and non-vesicular transport is a mechanism for directional lipid transport. Comparison of metabolic conversion and transport rates showed that non-vesicular transport dominates the organelle distribution of lipids, while species-specific phospholipid metabolism controls neutral lipid accumulation. Our results provide the first quantitative map of retrograde lipid flux in cells4. We anticipate that our pipeline for mapping of lipid flux through physical and chemical space in cells will boost our understanding of lipids in cell biology and disease.

生物化学工学
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