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

Author:

Bertolin Giulia12ORCID,Bulteau Anne-Laure345,Alves-Guerra Marie-Clotilde678,Burel Agnes9,Lavault Marie-Thérèse9,Gavard Olivia121011,Le Bras Stephanie12,Gagné Jean-Philippe11,Poirier Guy G11,Le Borgne Roland1210ORCID,Prigent Claude1210ORCID,Tramier Marc129ORCID

Affiliation:

1. CNRS, UMR 6290, Rennes, France

2. Université de Rennes 1, UBL, Genetics and Development Institute of Rennes (IGDR), Rennes, France

3. ENS de Lyon, Lyon, France

4. CNRS UMR 5242, Lyon, France

5. INRA USC 1370, Lyon, France

6. Inserm, U1016, Institut Cochin, Paris, France

7. CNRS, UMR 8104, Paris, France

8. Université Paris Descartes, Sorbonne Paris Cité, Paris, France

9. Microscopy Rennes Imaging Centre, SFR Biosit, UMS CNRS 3480- US INSERM 018, Université de Rennes, Rennes, France

10. Equipes labélisées Ligue Contre Le Cancer, Rennes, France

11. Centre de recherche du CHU de Québec, Faculté de Médecine, Université Laval, Québec, Canada

Abstract

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.

Funder

Association pour la Recherche sur le Cancer

Ligue Contre le Cancer

Fondation Tourre

Agence Nationale de la Recherche

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3