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Warburg-like Metabolic Reprogramming in Aging Intestinal Stem Cells Contributes to Tissue Hyperplasia
In many tissues, stem cell (SC) proliferation is dynamically adjusted to regenerative needs. How SCs adapt their metabolism to meet the demands of proliferation and how changes in such adaptive mechanisms contribute to age-related dysfunction remain poorly understood. Here, we identify mitochondrial...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011352/ https://www.ncbi.nlm.nih.gov/pubmed/33238124 http://dx.doi.org/10.1016/j.celrep.2020.108423 |
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author | Morris, Otto Deng, Hansong Tam, Christine Jasper, Heinrich |
author_facet | Morris, Otto Deng, Hansong Tam, Christine Jasper, Heinrich |
author_sort | Morris, Otto |
collection | PubMed |
description | In many tissues, stem cell (SC) proliferation is dynamically adjusted to regenerative needs. How SCs adapt their metabolism to meet the demands of proliferation and how changes in such adaptive mechanisms contribute to age-related dysfunction remain poorly understood. Here, we identify mitochondrial Ca(2+) uptake as a central coordinator of SC metabolism. Live imaging of genetically encoded metabolite sensors in intestinal SCs (ISCs) of Drosophila reveals that mitochondrial Ca(2+) uptake transiently adapts electron transport chain flux to match energetic demand upon proliferative activation. This tight metabolic adaptation is lost in ISCs of old flies, as declines in mitochondrial Ca(2+) uptake promote a “Warburg-like” metabolic reprogramming toward aerobic glycolysis. This switch mimics metabolic reprogramming by the oncogene Ras(V12) and enhances ISC hyperplasia. Our data identify a critical mechanism for metabolic adaptation of tissue SCs and reveal how its decline sets aging SCs on a metabolic trajectory reminiscent of that seen upon oncogenic transformation. |
format | Online Article Text |
id | pubmed-8011352 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
spelling | pubmed-80113522021-03-31 Warburg-like Metabolic Reprogramming in Aging Intestinal Stem Cells Contributes to Tissue Hyperplasia Morris, Otto Deng, Hansong Tam, Christine Jasper, Heinrich Cell Rep Article In many tissues, stem cell (SC) proliferation is dynamically adjusted to regenerative needs. How SCs adapt their metabolism to meet the demands of proliferation and how changes in such adaptive mechanisms contribute to age-related dysfunction remain poorly understood. Here, we identify mitochondrial Ca(2+) uptake as a central coordinator of SC metabolism. Live imaging of genetically encoded metabolite sensors in intestinal SCs (ISCs) of Drosophila reveals that mitochondrial Ca(2+) uptake transiently adapts electron transport chain flux to match energetic demand upon proliferative activation. This tight metabolic adaptation is lost in ISCs of old flies, as declines in mitochondrial Ca(2+) uptake promote a “Warburg-like” metabolic reprogramming toward aerobic glycolysis. This switch mimics metabolic reprogramming by the oncogene Ras(V12) and enhances ISC hyperplasia. Our data identify a critical mechanism for metabolic adaptation of tissue SCs and reveal how its decline sets aging SCs on a metabolic trajectory reminiscent of that seen upon oncogenic transformation. 2020-11-24 /pmc/articles/PMC8011352/ /pubmed/33238124 http://dx.doi.org/10.1016/j.celrep.2020.108423 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Morris, Otto Deng, Hansong Tam, Christine Jasper, Heinrich Warburg-like Metabolic Reprogramming in Aging Intestinal Stem Cells Contributes to Tissue Hyperplasia |
title | Warburg-like Metabolic Reprogramming in Aging Intestinal Stem Cells Contributes to Tissue Hyperplasia |
title_full | Warburg-like Metabolic Reprogramming in Aging Intestinal Stem Cells Contributes to Tissue Hyperplasia |
title_fullStr | Warburg-like Metabolic Reprogramming in Aging Intestinal Stem Cells Contributes to Tissue Hyperplasia |
title_full_unstemmed | Warburg-like Metabolic Reprogramming in Aging Intestinal Stem Cells Contributes to Tissue Hyperplasia |
title_short | Warburg-like Metabolic Reprogramming in Aging Intestinal Stem Cells Contributes to Tissue Hyperplasia |
title_sort | warburg-like metabolic reprogramming in aging intestinal stem cells contributes to tissue hyperplasia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011352/ https://www.ncbi.nlm.nih.gov/pubmed/33238124 http://dx.doi.org/10.1016/j.celrep.2020.108423 |
work_keys_str_mv | AT morrisotto warburglikemetabolicreprogramminginagingintestinalstemcellscontributestotissuehyperplasia AT denghansong warburglikemetabolicreprogramminginagingintestinalstemcellscontributestotissuehyperplasia AT tamchristine warburglikemetabolicreprogramminginagingintestinalstemcellscontributestotissuehyperplasia AT jasperheinrich warburglikemetabolicreprogramminginagingintestinalstemcellscontributestotissuehyperplasia |