Aurora kinase A localises to mitochondria to control organelle dynamics and energy production
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
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Author details
Funding
ARC (post-doc grant)
- Giulia Bertolin
Ligue Contre le Cancer (Grand ouest gant)
- Marc Tramier
Fondation Tourre (post-doc gant)
- Giulia Bertolin
Agence Nationale de la Recherche (KinBioFRET)
- Roland Le Borgne
- Claude Prigent
- Marc Tramier
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jody Rosenblatt, University of Utah, United States
Publication history
- Received: May 4, 2018
- Accepted: August 1, 2018
- Accepted Manuscript published: August 2, 2018 (version 1)
- Version of Record published: September 14, 2018 (version 2)
Copyright
© 2018, Bertolin et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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