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Nat Cell Biol. 2015 Oct;17(10):1304-16. doi: 10.1038/ncb3231. Epub 2015 Aug 31.

AMPK and PFKFB3 mediate glycolysis and survival in response to mitophagy during mitotic arrest.

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Cell Division and Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas, CSIC, E-28040 Madrid, Spain.
ICREA and Institute for Research in Biomedicine (IRB), Barcelona 08028, Spain.
Spectroscopy and Nuclear Magnetic Resonance Unit, CNIO, Madrid 28029, Spain.
Confocal Microscopy Unit, CNIO, Madrid  28029, Spain.
Division of Endocrinology, Diabetes & Nutrition, Boston University School of Medicine, Boston, Massachusetts 02215, USA.
Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela 15782, Spain.
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain.
Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, and Instituto de Investigaciones Sanitarias San Carlos (IdISSC), 28040 Madrid, Spain.
Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas, CSIC, E-28040 Madrid, Spain.


Blocking mitotic progression has been proposed as an attractive therapeutic strategy to impair proliferation of tumour cells. However, how cells survive during prolonged mitotic arrest is not well understood. We show here that survival during mitotic arrest is affected by the special energetic requirements of mitotic cells. Prolonged mitotic arrest results in mitophagy-dependent loss of mitochondria, accompanied by reduced ATP levels and the activation of AMPK. Oxidative respiration is replaced by glycolysis owing to AMPK-dependent phosphorylation of PFKFB3 and increased production of this protein as a consequence of mitotic-specific translational activation of its mRNA. Induction of autophagy or inhibition of AMPK or PFKFB3 results in enhanced cell death in mitosis and improves the anti-tumoral efficiency of microtubule poisons in breast cancer cells. Thus, survival of mitotic-arrested cells is limited by their metabolic requirements, a feature with potential implications in cancer therapies aimed to impair mitosis or metabolism in tumour cells.

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