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

作者：Domenech Elena; Maestre Carolina; Esteb An Martinez Lorena; Partidal David; Pascual Rosa; Fernandez Miranda Gonzalo; Seco Esther; Campos Olivas Ramon; Perez Manuel; Megias Diego; Allen Katherine; Lopez Miguel; Saha Asish K; Velasco Guillermo; Rial Eduardo; Mendez Raul; Boya Patricia; Salazar Roa Maria^*; Malumbres Marcos

来源：Nature Cell Biology, 2015, 17(10): 1304-+.

DOI：10.1038/ncb3231

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.

• 出版日期2015-10