Pantothenate kinase 4 controls skeletal muscle substrate metabolism

A Miranda-Cervantes; AM Fritzen; SH Raun; O Hodek; LLV Møller; K Johann; L Deisen; P Gregorevic; A Gudiksen; A Artati; J Adamski; NR Andersen; CM Sigvardsen; CS Carl; CT Voldstedlund; R Kjøbsted; SM Hauck; P Schjerling; TE Jensen; A Cebrian-Serrano; M Jähnert; P Gottmann; I Burtscher; H Lickert; H Pilegaard; A Schürmann; MH Tschöp; T Moritz; TD Müller; L Sylow; B Kiens; EA Richter; M Kleinert

Journal article

Pantothenate kinase 4 controls skeletal muscle substrate metabolism

A Miranda-Cervantes, AM Fritzen, SH Raun, O Hodek, LLV Møller, K Johann, L Deisen, P Gregorevic, A Gudiksen, A Artati, J Adamski, NR Andersen, CM Sigvardsen, CS Carl, CT Voldstedlund, R Kjøbsted, SM Hauck, P Schjerling, TE Jensen, A Cebrian-Serrano Show all

Nature Communications | Published : 2025

DOI: 10.1038/s41467-024-55036-w

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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 gluco..

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University of Melbourne Researchers

Paul Gregorevic Author

Related Projects (1)

USING GENE DELIVERY TECHNOLOGIES TO DEFINE NOVEL MECHANISMS OF SKELETAL MUSCLE ADAPTATION, AND DEVELOP MUSCLE-DIRECTED INTERVENTIONS FOR FRAILTY AND SERIOUS ILLNESS

The focus of my research is to investigate the cellular mechanisms underlying regulation of skeletal muscle size and function in health and ..

Grants

Awarded by Københavns Universitet

Funding Acknowledgements

The authors would like to acknowledge the critical input of J. F. P. Wojtaszewski (University of Copenhagen) and the assistance with AAV vector design and production of Dr J.R. Davey, Dr. K.I. Watt and Dr H. Qian (University of Melbourne). A.M.F. was supported by a postdoctoral research grant from the Danish Diabetes Academy and by the Novo Nordisk Foundation (grants NNF17SA0031406 and NNF22OC0074110). S.H.R. is funded by the Independent Research Fund Denmark (grant 2030-00007 A) and the Lundbeck Foundation (grant R380-2021-1451). L.L.V.M. is supported by the Lundbeck Foundation (grant R322-2019-2688). P.G. was supported by a Senior Research Fellowship (grant 1117835) and an Investigator Grant (grant 2017070) from the National Health and Medical Research Council of Australia. T.M. and O.H. are supported by the Novo Nordisk Foundation (grant NNF18CC0034900). T.D.M. received funding from the German Research Foundation (DFG TRR296, TRR152, SFB1123, and GRK 2816/1), the German Center for Diabetes Research, and the European Research Council (ERC-CoG Trusted grant no. 101044445). L.S. is supported by the Danish Council for Independent Research, Medical Sciences (grant DFF-4004-00233), and the Novo Nordisk Foundation (grants NNF16OC0023418 and NNF18OC0032082). E.A.R. is supported by the Novo Nordisk Foundation (grant NNF18OC0034072 II), the Independent Research Fund Denmark (grant DFF-7016-00147), and the Lundbeck Foundation (grant R233-2016-3566). M.K. is supported by the Deutsche Forschungsgemeinschaft (DFG grant KL 3285/2-1), the German Center for Diabetes Research (grants DZD 82DZD03D03 and 82DZD03D1Y), the Novo Nordisk Foundation (grant NNF19OC0055192), and the Lundbeck Foundation (grant R288-2018-78).