Luan Lin, Frederick Nathan P, Baskin Jeremy M
Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, New York, USA; email:
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, USA.
Annu Rev Biochem. 2025 Jun;94(1):417-446. doi: 10.1146/annurev-biochem-083024-110827. Epub 2025 Mar 18.
Lipids are a major class of biological molecules, the primary components of cellular membranes, and critical signaling molecules that regulate cell biology and physiology. Due to their dynamic behavior within membranes, rapid transport between organelles, and complex and often redundant metabolic pathways, lipids have traditionally been considered among the most challenging biological molecules to study. In recent years, a plethora of tools bridging the chemistry-biology interface has emerged for studying different aspects of lipid biology. Here, we provide an overview of these approaches. We discuss methods for lipid detection, including genetically encoded biosensors, synthetic lipid analogs, and metabolic labeling probes. For targeted manipulation of lipids, we describe pharmacological agents and controllable enzymes, termed membrane editors, that harness optogenetics and chemogenetics. To conclude, we survey techniques for elucidating lipid-protein interactions, including photoaffinity labeling and proximity labeling. Collectively, these strategies are revealing new insights into the regulation, dynamics, and functions of lipids in cell biology.
脂质是一类主要的生物分子,是细胞膜的主要成分,也是调节细胞生物学和生理学的关键信号分子。由于它们在膜内的动态行为、细胞器之间的快速运输以及复杂且往往冗余的代谢途径,脂质传统上被认为是最难研究的生物分子之一。近年来,出现了大量连接化学生物学界面的工具,用于研究脂质生物学的不同方面。在这里,我们概述这些方法。我们讨论脂质检测方法,包括基因编码生物传感器、合成脂质类似物和代谢标记探针。对于脂质的靶向操作,我们描述了利用光遗传学和化学遗传学的药物制剂和可控酶,即膜编辑器。最后,我们概述了阐明脂质-蛋白质相互作用的技术,包括光亲和标记和邻近标记。总的来说,这些策略正在揭示细胞生物学中脂质的调节、动态和功能的新见解。