News archives


OCTOBER - DECEMBER 17

JULY - SEPTEMBER 17

APRIL - JUNE 17

JANUARY - MARCH 17

OCTOBER - DECEMBER 16

JULY - SEPTEMBER 16

APRIL - JUNE 16

JANUARY - MARCH 16

OCTOBER - DECEMBER 15

JULY - SEPTEMBER 15

APRIL - JUNE 15

JANUARY - MARCH 15

OCTOBER - DECEMBER 14

JULY - SEPTEMBER 14

APRIL - JUNE 14

JANUARY - MARCH 14

OCTOBER - DECEMBER 13

JULY - SEPTEMBER 13

APRIL - JUNE 13

JANUARY - MARCH 13

OCTOBER - DECEMBER 12

JULY - SEPTEMBER 12

APRIL - JUNE 12

JANUARY - MARCH 12

OCTOBER - DECEMBER 11

JULY - SEPTEMBER 11

APRIL - JUNE 11

JANUARY - MARCH 11

OCTOBER - DECEMBER 10

JULY - SEPTEMBER 10

APRIL - JUNE 10

JANUARY - MARCH 10

OCTOBER - DECEMBER 09

JULY - SEPTEMBER 09

APRIL - JUNE 09

JANUARY - MARCH 09

OCTOBER - DECEMBER 08

JULY - SEPTEMBER 08

APRIL - JUNE 08

JANUARY - MARCH 08

OCTOBER - DECEMBER 07

JULY - SEPTEMBER 07

APRIL - JUNE 07

JANUARY - MARCH 07

 
  current news   Press   selected story    
     
  2nd September 2011  
 

NF-κB controls energy homeostasis and metabolic adaptation by upregulating mitochondrial respiration

 
 




Authors
Claudio Mauro1,4, Shi Chi Leow1,2,4, Elena Anso3, et. al.

1 - Section of Inflammation and Signal Transduction, Department of Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
2 - Laboratory of NF-κB Signaling, Proteos, Singapore 138673, Singapore.
3 - Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA.
4 - These authors contributed equally to this work.

Published in Nature Cell Biology, 28 August 2011 (Epub ahead of print)

Abstract
Cell proliferation is a metabolically demanding process. It requires active reprogramming of cellular bioenergetic pathways towards glucose metabolism to support anabolic growth. NF-κB/Rel transcription factors coordinate many of the signals that drive proliferation during immunity, inflammation and oncogenesis, but whether NF-κB regulates the metabolic reprogramming required for cell division during these processes is unknown. Here, we report that NF-κB organizes energy metabolism networks by controlling the balance between the utilization of glycolysis and mitochondrial respiration. NF-κB inhibition causes cellular reprogramming to aerobic glycolysis under basal conditions and induces necrosis on glucose starvation. The metabolic reorganization that results from NF-κB inhibition overcomes the requirement for tumour suppressor mutation in oncogenic transformation and impairs metabolic adaptation in cancer in vivo. This NF-κB-dependent metabolic pathway involves stimulation of oxidative phosphorylation through upregulation of mitochondrial synthesis of cytochrome c oxidase 2 (SCO2). Our findings identify NF-κB as a physiological regulator of mitochondrial respiration and establish a role for NF-κB in metabolic adaptation in normal cells and cancer.

 
 

 
 


Figure Legend : (NF-κB counters reprogramming to aerobic glycolysis and promotes metabolic adaptation to nutrient starvation. (ad) Glucose consumption (a, left), lactate production (b), ATP concentration (c) and oxygen consumption (d) in immortalized MEFs expressing non-specific (ns) or RelA-specific shRNAs, under normal culture conditions. (a), Right, western blots with the cells in ad, showing levels of RelA (knockdown efficiency), c-Rel and -actin (knockdown specificity). (e) Left, viability of immortalized MEFs expressing non-specific or RelA shRNAs after glucose starvation (GS). Middle, images of representative cells. Right, western blots with non-specific and RelA shRNA cells. Similar results were obtained using two additional non-specific shRNAs (ns2, shc003v), two additional RelA-specific shRNAs and eGFP-specific, luciferase-specific, laminA/C-specific and cyclophilinB-specific shRNAs. (fh) Lactate production (f), oxygen consumption (g) and ATP concentration (h) in cells treated as in e. Lactate values in f after day 4 should be interpreted with caution, owing to massive necrosis in RelA-shRNA cells. (i,j) Survival of the cells in e after 4-day glucose starvation, either alone (GS) or together with serum deprivation (GS+SD; i) or rapamycin (GS+Rapa; j, left). (j) Right, representative images. In aj the values denote means.e.m. n=3 (ac,e,f,hj); n=4 (d); n=10 (g). In h, *P<0.05; **P<0.01. Scale bars: 50 m.