Peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1α) is a metabolic regulator of intestinal epithelial cell fate

Ilenia D'Errico, Lorena Salvatore, Stefania Murzilli, Giuseppe Lo Sasso, Dominga Latorre, Nicola Martelli, Anastasia V. Egorova, Roman Polishuck, Katja Madeyski-Bengtson, Christopher Lelliott, Antonio J. Vidal-Puig, Peter Seibel, Gaetano Villani, Antonio Moschetta

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6603-6608
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number16
DOIs
StatePublished - Apr 19 2011

Keywords

  • Colon cancer
  • Medical physiology
  • Metabolism
  • Mitochondria
  • Nuclear receptors

ASJC Scopus subject areas

  • General

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  • Cite this

    D'Errico, I., Salvatore, L., Murzilli, S., Lo Sasso, G., Latorre, D., Martelli, N., Egorova, A. V., Polishuck, R., Madeyski-Bengtson, K., Lelliott, C., Vidal-Puig, A. J., Seibel, P., Villani, G., & Moschetta, A. (2011). Peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1α) is a metabolic regulator of intestinal epithelial cell fate. Proceedings of the National Academy of Sciences of the United States of America, 108(16), 6603-6608. https://doi.org/10.1073/pnas.1016354108