Aurora kinase A localises to mitochondria to control organelle dynamics and energy production

eLife

Agnes Burel¹  Stephanie Le Bras²  Marie-Thérèse Lavault³  Jean-Philippe Gagné⁴  Anne-Laure Bulteau⁵  Marc Tramier⁵  Giulia Bertolin⁶  Claude Prigent⁶  Marie-Clotilde Alves-Guerra⁷  Olivia Gavard⁸  Guy G Poirier⁹  Roland Le Borgne⁹ 

[1] CNRS UMR 5242, Lyon, France;CNRS, UMR 8104, Paris, France;INRA USC 1370, Lyon, France;Université Paris Descartes, Sorbonne Paris Cité, Paris, France;Université de Rennes 1, UBL, Genetics and Development Institute of Rennes (IGDR), Rennes, France;CNRS, UMR 6290, Rennes, France;ENS de Lyon, Lyon, France;Inserm, U1016, Institut Cochin, Paris, France;Microscopy Rennes Imaging Centre, SFR Biosit, UMS CNRS 3480- US INSERM 018, Université de Rennes, Rennes, France;

关键词: mitochondria;    cell cycle;    epithelial cancer;   

DOI  :  10.7554/eLife.38111

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown