马克斯·普朗克分子细胞生物学和遗传学研究所André Nadler小组近日取得一项新成果。经过不懈努力，他们的研究开发出了哺乳动物细胞脂质转运的定量成像。该项研究成果发表在2025年8月20日出版的《自然》上。

在这里，该研究组测量了哺乳动物细胞中单个脂质物种的逆行运输和代谢，主题是双功能脂质探针的时间分辨荧光成像，结合超高分辨率质谱和数学模型。细胞器间脂质通量的定量显示，定向的、非囊泡性的脂质转运负责快速的、物种选择性的脂质分选，而不是缓慢的、非特异性的囊泡膜转运。利用遗传扰动，该课题组研究人员发现能量依赖性脂质翻转和非囊泡转运之间的耦合是定向脂质转运的机制。代谢转化率和转运率的比较表明，非囊泡转运主导了脂质在细胞器中的分布，而物种特异性磷脂代谢控制中性脂质的积累。他们的结果提供了细胞中逆行脂质通量的第一个定量图谱。小组预计，他们通过细胞物理和化学空间绘制脂质通量的管道将促进他们对细胞生物学和疾病中的脂质的理解。

据了解，真核细胞产生超过1000种不同的脂质，它们调节细胞器膜特性，控制信号传导和储存能量。脂质如何在细胞器之间选择性分选以维持特定的膜特性在很大程度上是不清楚的，这是由于在细胞中脂质转运成像的困难。

附：英文原文

Title: Quantitative imaging of lipid transport in mammalian cells

Author: Iglesias-Artola, Juan M., Bhlig, Kristin, Schuhmann, Kai, Cook, Katelyn C., Lennartz, H. Mathilda, Schuhmacher, Milena, Barahtjan, Pavel, Jimnez Lpez, Cristina, achl, Radek, Garikapati, Vannuruswamy, Pombo-Garcia, Karina, Lohmann, Annett, Riegerov, Petra, Hof, Martin, Drobot, Bjrn, Shevchenko, Andrej, Honigmann, Alf, Nadler, Andr

Issue&Volume: 2025-08-20

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.

DOI: 10.1038/s41586-025-09432-x

Source: https://www.nature.com/articles/s41586-025-09432-x