title: Bax is necessary for PGC1α pro-apoptotic effect in colorectal cancer cells.
abstract: We have recently shown that the transcriptional coactivator PGC1α, a master regulator of mitochondrial biogenesis and function, is involved in the control of the intestinal epithelium cell fate. Furthermore, PGC1α protects against colon cancer formation by promoting ROS accumulation and, consequently, mitochondria-mediated apoptosis. Here we provide an additional mechanistic insight into the tumor suppressor activity of PGC1α showing that its pro-apoptotic effect is mediated by Bax. In fact, PGC1α overexpression in HCT116 Bax (-/-) colorectal cancer cells stimulates mitochondrial production and activity, but it fails to induce cell death as well as to oppose tumor growth in the xenograft model. The lack of ROS accumulation in the Bax (-/-) cells strengthens our view that the PGC1α-induced oxidative burst represents one of the main apoptosis-driving factors in colorectal cancer cells.
authors.affiliation: Laboratory of Lipid Metabolism, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy.
authors.forename: Ilenia
authors.initials: I
authors.lastname: D'Errico
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lo Sasso
authors.forename: Lorena
authors.initials: L
authors.lastname: Salvatore
authors.forename: Stefania
authors.initials: S
authors.lastname: Murzilli
authors.forename: Nicola
authors.initials: N
authors.lastname: Martelli
authors.forename: Maricarmen
authors.initials: M
authors.lastname: Cristofaro
authors.forename: Dominga
authors.initials: D
authors.lastname: Latorre
authors.forename: Gaetano
authors.initials: G
authors.lastname: Villani
authors.forename: Antonio
authors.initials: A
authors.lastname: Moschetta
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D004272:DNA, Mitochondrial / Q000032:analysis; D045325:HCT116 Cells; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst; D014157:Transcription Factors / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: C494826:BAX protein, human; D004272:DNA, Mitochondrial; D006360:Heat-Shock Proteins; D047495:PPAR gamma; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein