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

被引:72
作者
Bertolin, Giulia [1 ,2 ]
Bulteau, Anne-Laure [3 ,4 ,5 ]
Alves-Guerra, Marie-Clotilde [6 ,7 ,8 ]
Burel, Agnes [9 ]
Lavault, Marie-Therese [9 ]
Gavard, Olivia [1 ,2 ,10 ,11 ]
Le Bras, Stephanie [1 ,2 ]
Gagne, Jean-Philippe [11 ]
Poirier, Guy G. [11 ]
Le Borgne, Roland [1 ,2 ,10 ]
Prigent, Claude [1 ,2 ,10 ]
Tramier, Marc [1 ,2 ,9 ]
机构
[1] CNRS, UMR 6290, Rennes, France
[2] Univ Rennes 1, UBL, Genet & Dev Inst Rennes IGDR, Rennes, France
[3] ENS Lyon, Lyon, France
[4] CNRS, UMR 5242, Lyon, France
[5] INRA, USC 1370, Lyon, France
[6] INSERM, Inst Cochin, U1016, Paris, France
[7] CNRS, UMR 8104, Paris, France
[8] Univ Paris 05, Sorbonne Paris Cite, Paris, France
[9] Univ Rennes, Microscopy Rennes Imaging Ctr, UMS 3480, SFR Biosit,INSERM,CNRS,US 018,, Rennes, France
[10] Equipes Labelisees Ligue Canc, Rennes, France
[11] Univ Laval, Fac Med, Ctr Rech CHU Quebec, Quebec City, PQ, Canada
关键词
LARGE GENE LISTS; METABOLIC-REGULATION; BREAST-CANCER; CELL-CYCLE; FUSION; EXPRESSION; FISSION; INSTABILITY; MECHANISMS; PROTEASOME;
D O I
10.7554/eLife.38111
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
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 anticancer therapeutics based on the simultaneous targeting of mitochondrial functions and AURKA inhibition.
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页数:28
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