title: MondoA/ChREBP: The usual suspects of transcriptional glucose sensing; Implication in pathophysiology.
abstract: Identification of the Mondo glucose-responsive transcription factors family, including the MondoA and MondoB/ChREBP paralogs, has shed light on the mechanism whereby glucose affects gene transcription. They have clearly emerged, in recent years, as key mediators of glucose sensing by multiple cell types. MondoA and ChREBP have overlapping yet distinct expression profiles, which underlie their downstream targets and separate roles in regulating genes involved in glucose metabolism. MondoA can restrict glucose uptake and influences energy utilization in skeletal muscle, while ChREBP signals energy storage through de novo lipogenesis in liver and white adipose tissue. Because Mondo proteins mediate metabolic adaptations to changing glucose levels, a better understanding of cellular glucose sensing through Mondo proteins will likely uncover new therapeutic opportunities in the context of the imbalanced glucose homeostasis that accompanies metabolic diseases such as type 2 diabetes and cancer. Here, we provide an overview of structural homologies, transcriptional partners as well as the nutrient and hormonal mechanisms underlying Mondo proteins regulation. We next summarize their relative contribution to energy metabolism changes in physiological states and the evolutionary conservation of these pathways. Finally, we discuss their possible targeting in human pathologies.
authors.affiliation: Inserm, U1016, Institut Cochin, Paris, 75014, France; CNRS, UMR 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Richards
authors.affiliation: Inserm, U1016, Institut Cochin, Paris, 75014, France; CNRS, UMR 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Ourabah
authors.affiliation: Institut for Integrative Biology of the Cell (I2BC), CNRS, Université Paris-Sud, CEA, UMR 9198, F-91190, Gif-sur-Yvette, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Montagne
authors.affiliation: Inserm, U1016, Institut Cochin, Paris, 75014, France; CNRS, UMR 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Anne-Françoise
authors.initials: AF
authors.lastname: Burnol
authors.affiliation: Inserm, U1016, Institut Cochin, Paris, 75014, France; CNRS, UMR 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Postic
authors.affiliation: Inserm, U1016, Institut Cochin, Paris, 75014, France; CNRS, UMR 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France. Electronic address: sandra.guilmeau@inserm.fr.
authors.forename: Sandra
authors.initials: S
authors.lastname: Guilmeau
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D050155:Lipogenesis; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C550079:MondoA protein, mouse; D014157:Transcription Factors; D005947:Glucose
keywords: Cancer; ChREBP; Diabetes; Glucose and lipid metabolism; MondoA