PMID- 22351927
OWN - NLM
STAT- MEDLINE
DCOM- 20120501
LR  - 20230313
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 196
IP  - 4
DP  - 2012 Feb 20
TI  - IKKalpha and alternative NF-kappaB regulate PGC-1beta to promote oxidative muscle 
      metabolism.
PG  - 497-511
LID - 10.1083/jcb.201108118 [doi]
AB  - 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.
FAU - Bakkar, Nadine
AU  - Bakkar N
AD  - Department of Molecular Virology, Immunology, and Medical Genetics, Human Cancer 
      Genetics Program, The Ohio State University, Columbus, OH 43210, USA.
FAU - Ladner, Katherine
AU  - Ladner K
FAU - Canan, Benjamin D
AU  - Canan BD
FAU - Liyanarachchi, Sandya
AU  - Liyanarachchi S
FAU - Bal, Naresh C
AU  - Bal NC
FAU - Pant, Meghna
AU  - Pant M
FAU - Periasamy, Muthu
AU  - Periasamy M
FAU - Li, Qiutang
AU  - Li Q
FAU - Janssen, Paul M L
AU  - Janssen PM
FAU - Guttridge, Denis C
AU  - Guttridge DC
LA  - eng
GR  - R01 AR052787/AR/NIAMS NIH HHS/United States
GR  - AR052787/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (NF-kappa B)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppargc1a protein, mouse)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
SB  - IM
CIN - Nat Rev Mol Cell Biol. 2012 Apr;13(4):206. PMID: 22414895
MH  - Animals
MH  - Blotting, Western
MH  - *Cell Respiration
MH  - Cells, Cultured
MH  - Chromatin Immunoprecipitation
MH  - Electrophoretic Mobility Shift Assay
MH  - Gene Expression Regulation
MH  - I-kappa B Kinase/*metabolism
MH  - Immunoenzyme Techniques
MH  - Luciferases/metabolism
MH  - Mice
MH  - Mitochondria/metabolism
MH  - Muscle Development/*physiology
MH  - Muscle, Skeletal/cytology/*metabolism
MH  - Myoblasts/cytology/*metabolism
MH  - NF-kappa B/genetics/*metabolism
MH  - Oxidation-Reduction
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Trans-Activators/genetics/metabolism
MH  - Transcription Factors
PMC - PMC3284000
EDAT- 2012/02/22 06:00
MHDA- 2012/05/02 06:00
PMCR- 2012/08/20
CRDT- 2012/02/22 06:00
PHST- 2012/02/22 06:00 [entrez]
PHST- 2012/02/22 06:00 [pubmed]
PHST- 2012/05/02 06:00 [medline]
PHST- 2012/08/20 00:00 [pmc-release]
AID - jcb.201108118 [pii]
AID - 201108118 [pii]
AID - 10.1083/jcb.201108118 [doi]
PST - ppublish
SO  - J Cell Biol. 2012 Feb 20;196(4):497-511. doi: 10.1083/jcb.201108118.