Aurora kinase A localises to mitochondria to control organelle dynamics and energy production
2018
Giulia Bertolin | Anne-Laure Bulteau | Marie-Clotilde Alves-Guerra | Agnes Burel | Marie-Thérèse Lavault | Olivia Gavard | Stephanie Le Bras | Jean-Philippe Gagné | Guy G Poirier | Roland Le Borgne | Claude Prigent | Marc Tramier
Many epithelial cancers show cell cycle dysfunction tightly correlated with the overexpression of the serine/threonine kinase Aurora A (AURKA). Its role in mitotic progression has been extensively characterised, and evidence for new AURKA functions emerges. Here, we reveal that AURKA is located and imported in mitochondria in several human cancer cell lines. Mitochondrial AURKA impacts on two organelle functions: mitochondrial dynamics and energy production. When AURKA is expressed at endogenous levels during interphase, it induces mitochondrial fragmentation independently from RALA. Conversely, AURKA enhances mitochondrial fusion and ATP production when it is over-expressed. We demonstrate that AURKA directly regulates mitochondrial functions and that AURKA over-expression promotes metabolic reprogramming by increasing mitochondrial interconnectivity. Our work paves the way to anti-cancer therapeutics based on the simultaneous targeting of mitochondrial functions and AURKA inhibition.
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