Hodek, Ondrej
- Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences
- Swedish Metabolomics Centre
Research article2025Peer reviewedOpen access
Pantothenate kinase 4 controls skeletal muscle substrate metabolism
Miranda-Cervantes, Adriana; Fritzen, Andreas M.; Raun, Steffen H.; Hodek, Ondrej; Moller, Lisbeth L. V.; Johann, Kornelia; Deisen, Luisa; Gregorevic, Paul; Gudiksen, Anders; Artati, Anna; Adamski, Jerzy; Andersen, Nicoline R.; Sigvardsen, Casper M.; Carl, Christian S.; Voldstedlund, Christian T.; Kjobsted, Rasmus; Hauck, Stefanie M.; Schjerling, Peter; Jensen, Thomas E.; Cebrian-Serrano, Alberto; Jaehnert, Markus; Gottmann, Pascal; Burtscher, Ingo; Lickert, Heiko; Pilegaard, Henriette; Schuermann, Annette; Tschoep, Matthias H.; Moritz, Thomas; Mueller, Timo D.; Sylow, Lykke; Kiens, Bente; Richter, Erik A.; Kleinert, Maximilian
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Abstract
Metabolic flexibility in skeletal muscle is essential for maintaining healthy glucose and lipid metabolism, and its dysfunction is closely linked to metabolic diseases. Exercise enhances metabolic flexibility, making it an important tool for discovering mechanisms that promote metabolic health. Here we show that pantothenate kinase 4 (PanK4) is a new conserved exercise target with high abundance in muscle. Muscle-specific deletion of PanK4 impairs fatty acid oxidation which is related to higher intramuscular acetyl-CoA and malonyl-CoA levels. Elevated acetyl-CoA levels persist regardless of feeding state and are associated with whole-body glucose intolerance, reduced insulin-stimulated glucose uptake in glycolytic muscle, and impaired glucose uptake during exercise. Conversely, increasing PanK4 levels in glycolytic muscle lowers acetyl-CoA and enhances glucose uptake. Our findings highlight PanK4 as an important regulator of acetyl-CoA levels, playing a key role in both muscle lipid and glucose metabolism.
Published in
Nature Communications
2025, volume: 16, number: 1, article number: 345
Publisher: NATURE PORTFOLIO
SLU Authors
Moritz, Thomas
- Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences
- University of Copenhagen
- Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences
UKÄ Subject classification
Physiology and Anatomy
Publication identifier
- DOI: https://doi.org/10.1038/s41467-024-55036-w
Permanent link to this page (URI)
https://res.slu.se/id/publ/140199