| First Author | Bakkar N | Year | 2012 |
| Journal | J Cell Biol | Volume | 196 |
| Issue | 4 | Pages | 497-511 |
| PubMed ID | 22351927 | Mgi Jnum | J:181685 |
| Mgi Id | MGI:5313737 | Doi | 10.1083/jcb.201108118 |
| Citation | Bakkar N, et al. (2012) IKKalpha and alternative NF-kappaB regulate PGC-1beta to promote oxidative muscle metabolism. J Cell Biol 196(4):497-511 |
| abstractText | Although the physiological basis of canonical or classical IkappaB kinase beta (IKKbeta)-nuclear factor kappaB (NF-kappaB) signaling pathway is well established, how alternative NF-kappaB signaling functions beyond its role in lymphoid development remains unclear. In particular, alternative NF-kappaB signaling has been linked with cellular metabolism, but this relationship is poorly understood. In this study, we show that mice deleted for the alternative NF-kappaB components IKKalpha or RelB have reduced mitochondrial content and function. Conversely, expressing alternative, but not classical, NF-kappaB pathway components in skeletal muscle stimulates mitochondrial biogenesis and specifies slow twitch fibers, suggesting that oxidative metabolism in muscle is selectively controlled by the alternative pathway. The alternative NF-kappaB pathway mediates this specificity by direct transcriptional activation of the mitochondrial regulator PPAR-gamma coactivator 1beta (PGC-1beta) but not PGC-1alpha. Regulation of PGC-1beta by IKKalpha/RelB also is mammalian target of rapamycin (mTOR) dependent, highlighting a cross talk between mTOR and NF-kappaB in muscle metabolism. Together, these data provide insight on PGC-1beta regulation during skeletal myogenesis and reveal a unique function of alternative NF-kappaB signaling in promoting an oxidative metabolic phenotype. |
