Journal article

Compensatory regulation of HDAC5 in muscle maintains metabolic adaptive responses and metabolism in response to energetic stress

Sean L McGee, Courtney Swinton, Shona Morrison, Vidhi Gaur, Duncan E Campbell, Sebastian B Jorgensen, Bruce E Kemp, Keith Baar, Gregory R Steinberg, M Hargreaves

The FASEB Journal | FEDERATION AMER SOC EXP BIOL | Published : 2014

Abstract

Some gene deletions or mutations have little effect on metabolism and metabolic adaptation because of redundancy and/or compensation in metabolic pathways. The mechanisms for redundancy and/or compensation in metabolic adaptation in mammalian cells are unidentified. Here, we show that in mouse muscle and myogenic cells, compensatory regulation of the histone deacetylase (HDAC5) transcriptional repressor maintains metabolic integrity. HDAC5 phosphorylation regulated the expression of diverse metabolic genes and glucose metabolism in mouse C2C12 myogenic cells. However, loss of AMP-activated protein kinase (AMPK), a HDAC5 kinase, in muscle did not affect HDAC5 phosphorylation in mouse skeletal..

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Funding Acknowledgements

The authors thank Frosa Katsis (St. Vincent's Institute, Fitzroy, VIC, Australia) for the generation of HDAC5 and ACC phospho-specific antibodies and Professor Doreen Cantrell (The University of Dundee, Dundee, UK) for the PKD plasmids. This study was supported by grants from the Australia National Health and Medical Research Council (NHMRC) to S. L. M., B. E. K., and G. R. S. S. L. M. is supported by the Diabetes Australia Research Trust Viertel Award and a Career Development Fellowship from the NHMRC. Author contributions: S. L. M. and M. H. conceived the research; S. L. M., C. S., S. M., V. G., D. E. C., and S.B.J. performed experiments and analyzed data; B. E. K., K. B., and G. R. S. provided technical expertise and reagents; S. L. M. wrote the paper; all authors edited the paper and approved the final version.