Myogenin and class II HDACs control neurogenic muscle atrophy by inducing E3 ubiquitin ligases

Viviana Moresi, Andrew H. Williams, Eric Meadows, Jesse M. Flynn, Matthew J. Potthoff, John McAnally, John M. Shelton, Johannes Backs, William H. Klein, James A. Richardson, Rhonda Bassel-Duby, Eric N. Olson

Research output: Contribution to journalArticle

213 Citations (Scopus)

Abstract

Maintenance of skeletal muscle structure and function requires innervation by motor neurons, such that denervation causes muscle atrophy. We show that myogenin, an essential regulator of muscle development, controls neurogenic atrophy. Myogenin is upregulated in skeletal muscle following denervation and regulates expression of the E3 ubiquitin ligases MuRF1 and atrogin-1, which promote muscle proteolysis and atrophy. Deletion of myogenin from adult mice diminishes expression of MuRF1 and atrogin-1 in denervated muscle and confers resistance to atrophy. Mice lacking histone deacetylases (HDACs) 4 and 5 in skeletal muscle fail to upregulate myogenin and also preserve muscle mass following denervation. Conversely, forced expression of myogenin in skeletal muscle of HDAC mutant mice restores muscle atrophy following denervation. Thus, myogenin plays a dual role as both a regulator of muscle development and an inducer of neurogenic atrophy. These findings reveal a specific pathway for muscle wasting and potential therapeutic targets for this disorder.

Original languageEnglish (US)
Pages (from-to)35-45
Number of pages11
JournalCell
Volume143
Issue number1
DOIs
StatePublished - 2010

Fingerprint

Myogenin
Histone Deacetylases
Ubiquitin-Protein Ligases
Muscular Atrophy
Muscle
Skeletal Muscle
Denervation
Atrophy
Muscle Development
Muscles
Muscle Denervation
Motor Neurons
Proteolysis
Up-Regulation
Maintenance
Neurons

Keywords

  • Cellbio
  • Humdisease
  • Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Moresi, V., Williams, A. H., Meadows, E., Flynn, J. M., Potthoff, M. J., McAnally, J., ... Olson, E. N. (2010). Myogenin and class II HDACs control neurogenic muscle atrophy by inducing E3 ubiquitin ligases. Cell, 143(1), 35-45. https://doi.org/10.1016/j.cell.2010.09.004

Myogenin and class II HDACs control neurogenic muscle atrophy by inducing E3 ubiquitin ligases. / Moresi, Viviana; Williams, Andrew H.; Meadows, Eric; Flynn, Jesse M.; Potthoff, Matthew J.; McAnally, John; Shelton, John M.; Backs, Johannes; Klein, William H.; Richardson, James A.; Bassel-Duby, Rhonda; Olson, Eric N.

In: Cell, Vol. 143, No. 1, 2010, p. 35-45.

Research output: Contribution to journalArticle

Moresi, V, Williams, AH, Meadows, E, Flynn, JM, Potthoff, MJ, McAnally, J, Shelton, JM, Backs, J, Klein, WH, Richardson, JA, Bassel-Duby, R & Olson, EN 2010, 'Myogenin and class II HDACs control neurogenic muscle atrophy by inducing E3 ubiquitin ligases', Cell, vol. 143, no. 1, pp. 35-45. https://doi.org/10.1016/j.cell.2010.09.004
Moresi V, Williams AH, Meadows E, Flynn JM, Potthoff MJ, McAnally J et al. Myogenin and class II HDACs control neurogenic muscle atrophy by inducing E3 ubiquitin ligases. Cell. 2010;143(1):35-45. https://doi.org/10.1016/j.cell.2010.09.004
Moresi, Viviana ; Williams, Andrew H. ; Meadows, Eric ; Flynn, Jesse M. ; Potthoff, Matthew J. ; McAnally, John ; Shelton, John M. ; Backs, Johannes ; Klein, William H. ; Richardson, James A. ; Bassel-Duby, Rhonda ; Olson, Eric N. / Myogenin and class II HDACs control neurogenic muscle atrophy by inducing E3 ubiquitin ligases. In: Cell. 2010 ; Vol. 143, No. 1. pp. 35-45.
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