Mitophagy in mitosis: more than a myth

Work in the authors’ laboratories is funded by grants from MINECO (SAF2012-36079 to PB and SAF201238215, SAF2014-57791-REDC, and BFU2014-52125-REDT to MM), and Comunidad de Madrid (S2010/BMD2470).
An attractive strategy for cancer therapy is to stop cell proliferation by means of agents that directly arrest the cell cycle. Microtubule poisons such as taxanes block mitosis, eventually leading to cell death in a process frequently known as mitotic catastrophe. However, some cells are able to bypass this mitotic arrest and survive, thus contributing to chemoresistance to those therapies. We have recently observed that mitotic arrest induces an early autophagic flux response that results in autophagy-dependent mitochondrial degradation and a dramatic energetic deficit. The subsequent increase in the AMP/ATP ratio results in the activation of the metabolic sensor AMPK followed by phosphorylation and activation of PFKFB3, an enzyme required for glycolysis. Thus, mitophagy can be considered as a critical effector of the therapeutic effect of mitotic therapies, while both AMPK and PFKFB3 are critical for survival. The manipulation of these molecular routes may therefore have therapeutic benefits in the presence of microtubule poisons.
Depto. de Bioquímica y Biología Molecular
Fac. de Ciencias Biológicas
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