Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.
Nat Cell Biol
; 19(9): 1027-1036, 2017 Sep.
Article
em En
| MEDLINE
| ID: mdl-28812582
ABSTRACT
Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
/
Ácido Pirúvico
/
Proliferação de Células
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Drosophila melanogaster
/
Glicólise
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Mucosa Intestinal
/
Mitocôndrias
Idioma:
En
Revista:
Nat Cell Biol
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos