Mitochondria Mediate Tumor Necrosis Factor-α/NF-κB Signaling in Skeletal Muscle Myotubes

L. I. Yi-Ping, Coleen M. Atkins, J. David Sweatt, Michael B. Reid

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


Tumor necrosis factor-α (TNF-α) is implicated in muscle atrophy and weakness associated with a variety of chronic diseases. Recently, we reported that TNF-α directly induces muscle protein degradation in differentiated skeletal muscle myotubes, where it rapidly activates nuclear factor κB (NF-κB). We also have found that protein loss induced by TNF-α is NF-κB dependent. In the present study, we analyzed the signaling pathway by which TNF-α activates NF-κB in myotubes differentiated from C2C12 and rat primary myoblasts. We found that activation of NF-κB by TNF-α was blocked by rotenone or amytal, inhibitors of complex I of the mitochondrial respiratory chain. On the other hand, antimycin A, an inhibitor of complex III, enhanced TNF-α activation of NK-κB. These results suggest a key role of mitochondria-derived reactive oxygen species (ROS) in mediating NF-κB activation in muscle. In addition, we found that TNF-α stimulated protein kinase C (PKC) activity. However, other signal transduction mediators including ceramide, Ca2+, phospholipase A2 (PLA2), and nitric oxide (NO) do not appear to be involved in the activation of NF-κB.

Original languageEnglish (US)
Pages (from-to)97-104
Number of pages8
JournalAntioxidants and Redox Signaling
Issue number1
StatePublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology


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