Eintrag weiter verarbeiten
IKKα and alternative NF-κB regulate PGC-1β to promote oxidative muscle metabolism
Gespeichert in:
| Zeitschriftentitel: | Journal of Cell Biology |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , |
| In: | Journal of Cell Biology, 196, 2012, 4, S. 497-511 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Rockefeller University Press
|
| Schlagwörter: |
| Zusammenfassung: | <jats:p>Although the physiological basis of canonical or classical IκB kinase β (IKKβ)–nuclear factor κB (NF-κB) signaling pathway is well established, how alternative NF-κB signaling functions beyond its role in lymphoid development remains unclear. In particular, alternative NF-κB 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-κB components IKKα or RelB have reduced mitochondrial content and function. Conversely, expressing alternative, but not classical, NF-κB 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-κB pathway mediates this specificity by direct transcriptional activation of the mitochondrial regulator PPAR-γ coactivator 1β (PGC-1β) but not PGC-1α. Regulation of PGC-1β by IKKα/RelB also is mammalian target of rapamycin (mTOR) dependent, highlighting a cross talk between mTOR and NF-κB in muscle metabolism. Together, these data provide insight on PGC-1β regulation during skeletal myogenesis and reveal a unique function of alternative NF-κB signaling in promoting an oxidative metabolic phenotype.</jats:p> |
|---|---|
| Umfang: | 497-511 |
| ISSN: |
1540-8140
0021-9525 |
| DOI: | 10.1083/jcb.201108118 |