Cytosolic NUAK1 Enhances ATP Production by Maintaining Proper Glycolysis and Mitochondrial Function in Cancer Cells.
NUAK1
cancer metabolism
cell bioenergetic
glycolytic switch
mitochondrial donut
oxidative cells
seahorse assay
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2020
2020
Historique:
received:
01
04
2020
accepted:
04
06
2020
entrez:
6
8
2020
pubmed:
6
8
2020
medline:
6
8
2020
Statut:
epublish
Résumé
NUAK1 is an AMPK-related kinase located in the cytosol and the nucleus, whose expression associates with tumor malignancy and poor patient prognosis in several cancers. Accordingly, NUAK1 was associated with metastasis because it promotes cell migration and invasion in different cancer cells. Besides, NUAK1 supports cancer cell survival under metabolic stress and maintains ATP levels in hepatocarcinoma cells, suggesting a role in energy metabolism in cancer. However, the underlying mechanism for this metabolic function, as well as its link to NUAK1 subcellular localization, is unclear. We demonstrated that cytosolic NUAK1 increases ATP levels, which associates with increased mitochondrial respiration, supporting that cytosolic NUAK1 is involved in mitochondrial function regulation in cancer cells. NUAK1 inhibition led to the formation of "donut-like" structures, providing evidence of NUAK1-dependent mitochondrial morphology regulation. Additionally, our results indicated that cytosolic NUAK1 increases the glycolytic capacity of cancer cells under mitochondrial inhibition. Nuclear NUAK1 seems to be involved in the metabolic switch to glycolysis. Altogether, our results suggest that cytosolic NUAK1 participates in mitochondrial ATP production and the maintenance of proper glycolysis in cancer cells. Our current studies support the role of NUAK1 in bioenergetics, mitochondrial homeostasis, glycolysis and metabolic capacities. They suggest different metabolic outcomes depending on its subcellular localization. The identified roles of NUAK1 in cancer metabolism provide a potential mechanism relevant for tumor progression and its association with poor patient prognosis in several cancers. Further studies could shed light on the molecular mechanisms involved in the identified metabolic NUAK1 functions.
Identifiants
pubmed: 32754444
doi: 10.3389/fonc.2020.01123
pmc: PMC7367139
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1123Informations de copyright
Copyright © 2020 Escalona, Muñoz, Pincheira, Elorza and Castro.
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