RT Journal Article
T1 AMPK and PFKFB3 mediate glycolysis and survival in response to mitophagy during mitotic arrest
A1 Domenech, Elena
A1 Maestre, Carolina
A1 Esteban-Martínez, Lorena
A1 Partida, David
A1 Pascual, Rosa
A1 Fernández-Miranda, Gonzalo
A1 Seco, Esther
A1 Campos-Olivas, Ramón
A1 Pérez, Manuel
A1 Megias, Diego
A1 Allen, Katherine
A1 Lopez, Miguel
A1 Saha, Asish
A1 Velasco, Guillermo
A1 Rial, Eduardo
A1 Mendez, Raúl
A1 Boya, Patricia
A1 Salazar Roa, María
A1 Malumbres, Marcos
AB 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.
PB Nature Research
SN 1465-7392
YR 2015
FD 2015
LK https://hdl.handle.net/20.500.14352/95056
UL https://hdl.handle.net/20.500.14352/95056
LA eng
NO Doménech, E., Maestre, C., Esteban-Martínez, L. et al. AMPK and PFKFB3 mediate glycolysis and survival in response to mitophagy during mitotic arrest. Nat Cell Biol 17, 1304–1316 (2015). https://doi.org/10.1038/ncb3231
NO E.D., C.M. and M.S.-R. were supported by the Spanish Fondo de Investigaciones Sanitarias (Madrid), MINECO (Juan de la Cierva programme) and Asociación Española contra el Cáncer (AECC), respectively. L.E.-M. is a recipient of a JAE predoctoral fellowship from the CSIC. A.K.S. was supported by USPHS grants RO1DK19514, RO1DK67509. G.V. was supported by grants from the Spanish Ministry of Economy and Competitiveness (MINECO) and Fondo Europeo de Desarrollo Regional (FEDER) (PI12/02248), Fundació La Marató de TV3 (m12 20134031), and Fundación Mutua Madrileña (AP101042012). M.L. was supported by the European Community’s Seventh Framework Programme under grant agreement no. 281854—the ObERStress (European Research Council project). E.R. was financially supported by a MINECO grant (SAF 2010-20256). Work in the R.M. laboratory was supported by the Fundación Botín, Banco Santander and MINECO (BFU2011-30121, BFU2014-52125-REDT and Consolider RNAREG CSD2009-00080). Work in the P.B. laboratory is supported by a grant from the Spanish Ministry for Economy and Competitiveness (MINECO; SAF2012-36079). Work in the M.M. laboratory was supported by grants from the MINECO (SAF2012-38215), Consolider-Ingenio 2010 Programme (SAF2014-57791-REDC), Excellence Network CellSYS (BFU2014-52125-REDT), the OncoCycle Programme (S2010/BMD-2470) from the Comunidad de Madrid, Worldwide Cancer Research (WCR no. 15-0278), and the European Union Seventh Framework Programme (MitoSys project; HEALTH-F5-2010-241548).
NO Asociación Española contra el Cáncer
NO Fundació La Marató de TV3
NO Fundación Mutua Madrileña
NO Comunidad de Madrid
NO Ministerio de Economía y Competitividad (España)
NO European Commission
DS Docta Complutense
RD 15 jun 2025