title: Peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC1alpha) is a metabolic regulator of intestinal epithelial cell fate.
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.
authors.affiliation: Laboratory of Lipid Metabolism and Cancer, Department of Translational Pharmacology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Chieti, Italy.
authors.forename: Ilenia
authors.initials: I
authors.lastname: D'Errico
authors.forename: Lorena
authors.initials: L
authors.lastname: Salvatore
authors.forename: Stefania
authors.initials: S
authors.lastname: Murzilli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lo Sasso
authors.forename: Dominga
authors.initials: D
authors.lastname: Latorre
authors.forename: Nicola
authors.initials: N
authors.lastname: Martelli
authors.forename: Anastasia V
authors.initials: AV
authors.lastname: Egorova
authors.forename: Roman
authors.initials: R
authors.lastname: Polishuck
authors.forename: Katja
authors.initials: K
authors.lastname: Madeyski-Bengtson
authors.forename: Christopher
authors.initials: C
authors.lastname: Lelliott
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Vidal-Puig
authors.forename: Peter
authors.initials: P
authors.lastname: Seibel
authors.forename: Gaetano
authors.initials: G
authors.lastname: Villani
authors.forename: Antonio
authors.initials: A
authors.lastname: Moschetta
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D020895:Enterocytes / Q000378:metabolism* / Q000473:pathology; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010101:Oxygen Consumption / Q000235:genetics; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D006360:Heat-Shock Proteins; D009363:Neoplasm Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors