Mottillo_2023_Cell.Rep.Methods_3_100394

Reference

Title : A FRET sensor for the real-time detection of long chain acyl-CoAs and synthetic ABHD5 ligands - Mottillo_2023_Cell.Rep.Methods_3_100394
Author(s) : Mottillo EP , Mladenovic-Lucas L , Zhang H , Zhou L , Kelly CV , Ortiz PA , Granneman JG
Ref : Cell Rep Methods , 3 :100394 , 2023
Abstract : Intracellular long-chain acyl-coenzyme As (LC-acyl-CoAs) are thought to be under tight spatial and temporal controls, yet the ability to image LC-acyl-CoAs in live cells is lacking. Here, we developed a fluorescence resonance energy transfer (FRET) sensor for LC-acyl-CoAs based on the allosterically regulated interaction between alpha/beta hydrolase domain-containing 5 (ABHD5) and Perilipin 5. The genetically encoded sensor rapidly detects intracellular LC-acyl-CoAs generated from exogenous and endogenous fatty acids (FAs), as well as synthetic ABHD5 ligands. Stimulation of lipolysis in brown adipocytes elevated intracellular LC-acyl-CoAs in a cyclic fashion, which was eliminated by inhibiting PNPLA2 (ATGL), the major triglyceride lipase. Interestingly, inhibition of LC-acyl-CoA transport into mitochondria elevated intracellular LC-acyl-CoAs and dampened their cycling. Together, these observations reveal an intimate feedback control between LC-acyl-CoA generation from lipolysis and utilization in mitochondria. We anticipate that this sensor will be an important tool to dissect intracellular LC-acyl-CoA dynamics as well to discover novel synthetic ABHD5 ligands.
ESTHER : Mottillo_2023_Cell.Rep.Methods_3_100394
PubMedSearch : Mottillo_2023_Cell.Rep.Methods_3_100394
PubMedID: 36936069
Gene_locus related to this paper: human-ABHD5

Related information

Gene_locus related to this paper: human-ABHD5

Citations formats

Mottillo EP, Mladenovic-Lucas L, Zhang H, Zhou L, Kelly CV, Ortiz PA, Granneman JG (2023)
A FRET sensor for the real-time detection of long chain acyl-CoAs and synthetic ABHD5 ligands
Cell Rep Methods 3 :100394

Mottillo EP, Mladenovic-Lucas L, Zhang H, Zhou L, Kelly CV, Ortiz PA, Granneman JG (2023)
Cell Rep Methods 3 :100394