Membrane Topology of Trafficking Regulator of GLUT4 1 (TRARG1).
Duan et al. describe the membrane topology of trafficking regulator of GLUT1 (TRARG1; formally known as TUSC5). We previously identified TRARG1 as a regulator of GLUT4 trafficking in 2015 (click here)
Duan X, Krycer JR, Cooke KC, Yang G, James DE, Fazakerley DJ.
Muscle and adipose tissue insulin resistance: malady without mechanism?
Fazakerley, Krycer et al. review mechanisms of muscle and adipose insulin resistance.
Fazakerley DJ, Krycer JR, Kearney AL, Hocking SL, James DE.
Mitochondrial oxidative stress causes insulin resistance without disrupting oxidative phosphorylation.
Our collaboration with Mike Murphy (University of Cambridge) and Richard Hartley (University of Glasgow) using a novel compound to show that mitochondrial oxidative stress rapidly induces insulin resistance independently of changes in mitochondrial respiration.
Fazakerley DJ, Minard AY, Krycer JR, Thomas KC, Stöckli J, Harney DJ, Burchfield JG, Maghzal GJ, Caldwell ST, Hartley RC, Stocker R, Murphy MP, James DE.
Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance.
Fazakerley et al. identify that loss of mitochondrial CoQ is a proximal driver of mitochondrial oxidants and insulin resistance.
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Fazakerley DJ, Chaudhuri R, Yang P, Maghzal GJ, Thomas KC, Krycer JR, Humphrey SJ, Parker BL, Fisher-Wellman KH, Meoli CC, Hoffman NJ, Diskin C, Burchfield JG, Cowley MJ, Kaplan W, Modrusan Z, Kolumam G, Yang JY, Chen DL, Samocha-Bonet D, Greenfield JR, Hoehn KL, Stocker R, James DE.
A gas trapping method for high-throughput metabolic experiments
Krycer et al. developed a novel gas-trapping method for high-throughput metabolic experiments. Adapted for cells grown in 12- or 24-well plates, this can be used to measure substrate oxidation by collecting CO2 or hydrogen sulphide production from cysteine metabolism.
Krycer JR, Diskin C, Nelson ME, Zeng XY, Fazakerley DJ, James DE
The transcriptional response to oxidative stress is part of, but not sufficient for, insulin resistance in adipocytes
It is well-established that reactive oxygen species (ROS) are linked to insulin resistance. Chaudhuri, Krycer et al. found that although ROS induces substantial changes across the transcriptional landscape in adipocytes, this transcriptional response is not required for ROS to cause insulin resistance. This suggests that ROS acts via other ‘omes, such as post-translational modifications, to cause insulin resistance in adipocytes.
Chaudhuri R, Krycer JR, Fazakerley DJ, Fisher-Wellman KH, Su Z, Hoehn KL, Yang JYH, Kuncic Z, Vafaee F, James DE.
Dynamic Metabolomics Reveals that Insulin Primes the Adipocyte for Glucose Metabolism
Krycer et al. explored how insulin regulates adipocyte metabolism. It is widely-held that energy storage (anabolism) occurs as a substrate accumulates. However, using dynamic tracer metabolomics and overlaying phosphoproteomics data, they found insulin signalling triggers anabolism before substrates accumulated, creating a ‘demand-driven’ system to prime adipocytes for glucose metabolism.
Krycer JR, Yugi K, Hirayama A, Fazakerley DJ, Quek LE, Scalzo R, Ohno S, Hodson MP, Ikeda S, Shoji F, Suzuki K, Domanova W, Parker BL, Nelson ME, Humphrey SJ, Turner N, Hoehn KL, Cooney GJ, Soga T, Kuroda S, James DE
Editor's pick at JBC!
Metabolomic analysis of insulin resistance across different mouse strains and diets
"Insulin resistance is a complex condition with many genetic and environmental determinants. Stöckli et al carried out a comprehensive metabolomic analysis of three different mouse strains on high-fat or standard diets. The analysis showed that, despite individual, environmental, and genetic variation, a combination of three metabolites (C22:1-CoA, C2-carnitine, and C16-ceramide) together formed an accurate signature for predicting insulin resistance."
Jacqueline Stöckli, Kelsey H. Fisher-Wellman, Rima Chaudhuri, Xiao-Yi Zeng, Daniel J. Fazakerley, Christopher C. Meoli, Kristen C. Thomas, Nolan J. Hoffman, Salvatore P. Mangiafico, Chrysovalantou E. Xirouchaki, Chieh-Hsin Yang, Olga Ilkayeva, Kari Wong, Gregory J. Cooney, Sofianos Andrikopoulos, Deborah M. Muoio, and David E. James
Multiplexed Temporal Quantification of the Exercise-regulated Plasma Peptidome
The latest paper by Parker et al. has been one the most highly viewed article of the Journal of Molecular & Cellular Proteomics during the past month!
Benjamin L. Parker, James G. Burchfield, Daniel Clayton, Thomas A. Geddes, Richard J. Payne, Bente Kiens, Jørgen F. P. Wojtaszewski, Erik A. Richter and David E. James