光触媒近接標識戦略を開発、細胞小器官選択的な脂質解析を実現(Researchers Develop Photocatalytic Proximity Labeling Strategy for Organelle-selective Lipid Analysis)

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2025-08-07 中国科学院(CAS)

中国科学院上海有機化学研究所の朱正江教授と陳宜雲教授らは、細胞小器官ごとの脂質を質量分析で選択的に解析できる「光触媒近接標識法」を開発した(Nature Chemistry掲載)。脂質構造に基づき設計した光触媒標識プローブを、特定の小器官に局在する有機色素で青色光照射下に活性化し、その場で脂質を標識する。液クロ-MS解析により小器官分離なしで標識脂質を検出し、ミトコンドリア・核・リソソームで計60〜80種(7主要脂質クラス)を同定した。さらに安定同位体トレーシングと組み合わせ、ERから他小器官への脂質輸送速度や経路を定量化。VPS13AとPDZD8が脂肪酸鎖特異的なER-ミトコンドリア輸送に重要で、mTOR活性化がリソソームのコレステロールやPE、PSを選択的に増加させることも解明した。

<関連情報>

オルガネラ間の脂質輸送の定量的なプロファイリングを、細胞内光触媒標識法により実現 Quantitative profiling of lipid transport between organelles enabled by subcellular photocatalytic labelling

Xi Chen,Ru He,Haolin Xiong,Ruohong Wang,Yandong Yin,Yiyun Chen & Zheng-Jiang Zhu
Nature Chemistry  Published:06 August 2025
DOI:https://doi.org/10.1038/s41557-025-01886-w

光触媒近接標識戦略を開発、細胞小器官選択的な脂質解析を実現(Researchers Develop Photocatalytic Proximity Labeling Strategy for Organelle-selective Lipid Analysis)

Abstract

Subcellular lipid composition and transport substantially influence the physiological and pathological functions of both cells and organelles. However, lipid transport and turnover between organelles remain poorly understood due to a lack of methods for selectively labelling lipids in organelles. Here we develop a subcellular photocatalytic labelling strategy that enables organelle-selective lipid analysis by mass spectrometry and the quantitative profiling of lipid transport between organelles. We use this approach to quantitatively characterize fatty-acyl-dependent transport of phosphatidylethanolamine and phosphatidylserine lipids between the endoplasmic reticulum and mitochondria, the nucleus or lysosomes. Further experiments revealed the relative contributions of various biosynthesis pathways to the phosphatidylethanolamine and phosphatidylserine lipid compositions in the mitochondria, nucleus and lysosomes. Lysosome-specific photocatalytic labelling revealed the impact of the mTOR kinase pathway on lysosomal lipid metabolism. Together, this subcellularly localized photocatalytic labelling of lipids quantitatively deciphers the subcellular lipid composition and transport, enhancing our understanding of lipid metabolism in living organisms.

生物化学工学
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