ArticleACS chemical biology2024
Imaging Interorganelle Phospholipid Transport by Extended Synaptotagmins Using Bioorthogonally Tagged Lipids.
Article in ACS chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Bioorthogonal chemistry for deciphering lipid biology in living systems.RSC chemical biology · 2026Review
- Advanced imaging of membrane contact sites.Nature cell biology · 2026Review
- Chemical biology approaches for revealing interorganelle lipid transport pathways.Current opinion in cell biology · 2026Review
- A Fluorogenic Hydrazino-Pictet-Spengler Reaction in Live Cells.Angewandte Chemie (International ed. in English) · 2025Article
- Emerging Approaches for Studying Lipid Dynamics, Metabolism, and Interactions in Cells.Annual review of biochemistry · 2025Review
- Synthetic Lipid Biology.Chemical reviews · 2025Review
- Nonlinear dynamics in phosphoinositide metabolism.Current opinion in cell biology · 2024Review
- Ultralow Background Membrane Editors for Spatiotemporal Control of Phosphatidic Acid Metabolism and Signaling.ACS central science · 2024Article
- Chemical Approaches for Measuring and Manipulating Lipids at the Organelle Level.Cold Spring Harbor perspectives in biology · 2023Review
- Ultralow background membrane editors for spatiotemporal control of lipid metabolism and signaling.bioRxiv : the preprint server for biology · 2023Article
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Authors and funding
5 authors.
Funding
Abstract
The proper distribution of lipids within organelle membranes requires rapid interorganelle lipid transport, much of which occurs at membrane contact sites and is mediated by lipid transfer proteins (LTPs). Our current understanding of LTP mechanism and function is based largely on structural studies and in vitro reconstitution. Existing cellular assays for LTP function use indirect readouts, and it remains an open question as to whether substrate specificity and transport kinetics established in vitro are similar in cellular settings. Here, we harness bioorthogonal chemistry to develop tools for direct visualization of interorganelle transport of phospholipids between the plasma membrane (PM) and the endoplasmic reticulum (ER). Unnatural fluorescent phospholipid analogs generated by the transphosphatidylation activity of phospholipase D (PLD) at the PM are rapidly transported to the ER dependent in part upon extended synaptotagmins (E-Syts), a family of LTPs at ER-PM contact sites. Ectopic expression of an artificial E-Syt-based tether at ER-mitochondria contact sites results in fluorescent phospholipid accumulation in mitochondria. Finally, in vitro reconstitution assays demonstrate that the fluorescent lipids are bona fide E-Syt substrates. Thus, fluorescent lipids generated in situ via PLD activity and bioorthogonal chemical tagging can enable direct visualization of the activity of LTPs that mediate bulk phospholipid transport at ER-PM contact sites.
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Registered trials
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