Title

「Tracking inter-organelle lipid flux via organelle-specific isotope labeling and detection」 ポスター🔗

Lecturer

Dr. Masaaki Uematsu(Cornell University・M.D.,Ph.D.)

Date, Time & Venue

16:15-17:15 , November 20 , 2025 Seminar Room A , 2nd floor the Building G , Medical Campus

Abstract

Lipids are essential in defining organelle boundaries that enable compartmentalized biological reactions. Although continuous lipid synthesis, degradation, and transport are important for organelle homeostasis, tracking these dynamics—especially inter-organelle lipid transport—is difficult because biochemical isolation of organelle lipids compromises spatial resolution and quantification. Alternative approaches—such as chemically installing fluorophores or small chemical handles, or expressing genetically encoded lipid-binding probes—often perturb lipid function and localization. To overcome these limitations, I developed a minimally perturbative method to measure inter-organelle transport of phosphatidylcholine (PC), the most abundant phospholipid in mammalian cells, with high spatiotemporal resolution. Using phospholipase D (PLD), I established an organelle-specific labeling system that converts endogenous PC into deuterated PC. PLD was engineered to be light-activatable, enabling precise pulse labeling. When combined with a second, drug-activatable PLD, the platform enables detection of the transported, labeled PC on another organelle, quantifying PC flux between any desired pair of organelles. It can also be applied to absolute quantification and turnover measurements of organelle PC. Finally, I introduce AI-driven protein design to extend the approach to other lipid classes beyond PC by tuning PLD substrate preferences. Together, these advances are expected to enable a quantitative, systems-level understanding of intracellular lipid transport.

Contact

Division of Integrated Life Science, Department of Gene Mechanisms,

Laboratory of Cell Cycle Regulation

Center for Living Systems Information Science 【CeLiSIS】
Kazuhiro Aoki(aoki.kazuhiro.6v@kyoto-u.ac.jp