TY - JOUR
T1 - Peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1α) is a metabolic regulator of intestinal epithelial cell fate
AU - D'Errico, Ilenia
AU - Salvatore, Lorena
AU - Murzilli, Stefania
AU - Lo Sasso, Giuseppe
AU - Latorre, Dominga
AU - Martelli, Nicola
AU - Egorova, Anastasia V.
AU - Polishuck, Roman
AU - Madeyski-Bengtson, Katja
AU - Lelliott, Christopher
AU - Vidal-Puig, Antonio J.
AU - Seibel, Peter
AU - Villani, Gaetano
AU - Moschetta, Antonio
PY - 2011/4/19
Y1 - 2011/4/19
N2 - Peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1α) is a transcriptional coactivator able to up-regulate mitochondrial biogenesis, respiratory capacity, oxidative phosphorylation, and fatty acid β-oxidation with the final aim of providing a more efficient pathway for aerobic energy production. In the continuously renewed intestinal epithelium, proliferative cells in the crypts migrate along the villus axis and differentiate into mature enterocytes, increasing their respiratory capacity and finally undergoing apoptosis. Here we show that in the intestinal epithelial surface, PGC1α drives mitochondrial biogenesis and respiration in the presence of reduced antioxidant enzyme activities, thus determining the accumulation of reactive oxygen species and fostering the fate of enterocytes toward apoptosis. Combining gain- and loss-of-function genetic approaches in human cells and mouse models of intestinal cancer, we present an intriguing scenario whereby PGC1α regulates enterocyte cell fate and protects against tumorigenesis.
AB - Peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1α) is a transcriptional coactivator able to up-regulate mitochondrial biogenesis, respiratory capacity, oxidative phosphorylation, and fatty acid β-oxidation with the final aim of providing a more efficient pathway for aerobic energy production. In the continuously renewed intestinal epithelium, proliferative cells in the crypts migrate along the villus axis and differentiate into mature enterocytes, increasing their respiratory capacity and finally undergoing apoptosis. Here we show that in the intestinal epithelial surface, PGC1α drives mitochondrial biogenesis and respiration in the presence of reduced antioxidant enzyme activities, thus determining the accumulation of reactive oxygen species and fostering the fate of enterocytes toward apoptosis. Combining gain- and loss-of-function genetic approaches in human cells and mouse models of intestinal cancer, we present an intriguing scenario whereby PGC1α regulates enterocyte cell fate and protects against tumorigenesis.
KW - Colon cancer
KW - Medical physiology
KW - Metabolism
KW - Mitochondria
KW - Nuclear receptors
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UR - http://www.scopus.com/inward/citedby.url?scp=79955634801&partnerID=8YFLogxK
U2 - 10.1073/pnas.1016354108
DO - 10.1073/pnas.1016354108
M3 - Article
C2 - 21467224
AN - SCOPUS:79955634801
SN - 0027-8424
VL - 108
SP - 6603
EP - 6608
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 16
ER -