In:
PLOS Biology, Public Library of Science (PLoS), Vol. 20, No. 6 ( 2022-6-10), p. e3001678-
Abstract:
Cells must adjust the expression levels of metabolic enzymes in response to fluctuating nutrient supply. For glucose, such metabolic remodeling is highly dependent on a master transcription factor ChREBP/MondoA. However, it remains elusive how glucose fluctuations are sensed by ChREBP/MondoA despite the stability of major glycolytic pathways. Here, we show that in both flies and mice, ChREBP/MondoA activation in response to glucose ingestion involves an evolutionarily conserved glucose-metabolizing pathway: the polyol pathway. The polyol pathway converts glucose to fructose via sorbitol. It has been believed that this pathway is almost silent, and its activation in hyperglycemic conditions has deleterious effects on human health. We show that the polyol pathway regulates the glucose-responsive nuclear translocation of Mondo, a Drosophila homologue of ChREBP/MondoA, which directs gene expression for organismal growth and metabolism. Likewise, inhibition of the polyol pathway in mice impairs ChREBP’s nuclear localization and reduces glucose tolerance. We propose that the polyol pathway is an evolutionarily conserved sensing system for glucose uptake that allows metabolic remodeling.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3001678
DOI:
10.1371/journal.pbio.3001678.g001
DOI:
10.1371/journal.pbio.3001678.g002
DOI:
10.1371/journal.pbio.3001678.g003
DOI:
10.1371/journal.pbio.3001678.g004
DOI:
10.1371/journal.pbio.3001678.g005
DOI:
10.1371/journal.pbio.3001678.g006
DOI:
10.1371/journal.pbio.3001678.s001
DOI:
10.1371/journal.pbio.3001678.s002
DOI:
10.1371/journal.pbio.3001678.s003
DOI:
10.1371/journal.pbio.3001678.s004
DOI:
10.1371/journal.pbio.3001678.s005
DOI:
10.1371/journal.pbio.3001678.s006
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10.1371/journal.pbio.3001678.s007
DOI:
10.1371/journal.pbio.3001678.s008
DOI:
10.1371/journal.pbio.3001678.s009
DOI:
10.1371/journal.pbio.3001678.s010
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10.1371/journal.pbio.3001678.s011
DOI:
10.1371/journal.pbio.3001678.s012
DOI:
10.1371/journal.pbio.3001678.s013
DOI:
10.1371/journal.pbio.3001678.s014
DOI:
10.1371/journal.pbio.3001678.s015
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10.1371/journal.pbio.3001678.s016
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10.1371/journal.pbio.3001678.s017
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10.1371/journal.pbio.3001678.s018
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10.1371/journal.pbio.3001678.s019
DOI:
10.1371/journal.pbio.3001678.s020
DOI:
10.1371/journal.pbio.3001678.s021
DOI:
10.1371/journal.pbio.3001678.s022
DOI:
10.1371/journal.pbio.3001678.s023
DOI:
10.1371/journal.pbio.3001678.r001
DOI:
10.1371/journal.pbio.3001678.r002
DOI:
10.1371/journal.pbio.3001678.r003
DOI:
10.1371/journal.pbio.3001678.r004
DOI:
10.1371/journal.pbio.3001678.r005
DOI:
10.1371/journal.pbio.3001678.r006
DOI:
10.1371/journal.pbio.3001678.r007
DOI:
10.1371/journal.pbio.3001678.r008
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2126773-X
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