Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

IKK/NF-κB Regulates Skeletal Myogenesis via a Signaling Switch to Inhibit Differentiation and Promote Mitochondrial Biogenesis

Nadine Bakkar, Jingxin Wang, Katherine J. Ladner, Huating Wang, Jason M. Dahlman, Michael Carathers, Swarnali Acharyya, Michael A. Rudnicki, Andrew D. Hollenbach and Denis C. Guttridge
The Journal of Cell Biology
Vol. 180, No. 4 (Feb. 25, 2008), pp. 787-802
Stable URL: http://www.jstor.org/stable/20475818
Page Count: 16
  • More info
  • Cite this Item
IKK/NF-κB Regulates Skeletal Myogenesis via a Signaling Switch to Inhibit Differentiation and Promote Mitochondrial Biogenesis
Preview not available

Abstract

Nuclear factor κB (NF-κB) is involved in multiple skeletal muscle disorders, but how it functions in differentiation remains elusive given that both anti- and promyogenic activities have been described. In this study, we resolve this by showing that myogenesis is controlled by opposing NF-κB signaling pathways. We find that myogenesis is enhanced in MyoD-expressing fibroblasts deficient in classical pathway components RelA/p65, inhibitor of κB kinase β (IKKβ), or IKKγ. Similar increases occur in myoblasts lacking RelA/p65 or IKKβ, and muscles from RelA/p65 or IKKβ mutant mice also contain higher fiber numbers. Moreover, we show that during differentiation, classical NF-κB signaling decreases, whereas the induction of alternative members IKKα, RelB, and p52 occurs late in myogenesis. Myotube formation does not require alternative signaling, but it is important for myotube maintenance in response to metabolic stress. Furthermore, overexpression or knockdown of IKKα regulates mitochondrial content and function, suggesting that alternative signaling stimulates mitochondrial biogenesis. Together, these data reveal a unique IKK/NF-κB signaling switch that functions to both inhibit differentiation and promote myotube homeostasis.

Page Thumbnails

  • Thumbnail: Page 
787
    787
  • Thumbnail: Page 
788
    788
  • Thumbnail: Page 
789
    789
  • Thumbnail: Page 
790
    790
  • Thumbnail: Page 
791
    791
  • Thumbnail: Page 
792
    792
  • Thumbnail: Page 
793
    793
  • Thumbnail: Page 
794
    794
  • Thumbnail: Page 
795
    795
  • Thumbnail: Page 
796
    796
  • Thumbnail: Page 
797
    797
  • Thumbnail: Page 
798
    798
  • Thumbnail: Page 
799
    799
  • Thumbnail: Page 
800
    800
  • Thumbnail: Page 
801
    801
  • Thumbnail: Page 
802
    802