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

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...

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Autores principales: Bertolin, Giulia, Bulteau, Anne-Laure, Alves-Guerra, Marie-Clotilde, Burel, Agnes, Lavault, Marie-Thérèse, Gavard, Olivia, Le Bras, Stephanie, Gagné, Jean-Philippe, Poirier, Guy G, Le Borgne, Roland, Prigent, Claude, Tramier, Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140714/
https://www.ncbi.nlm.nih.gov/pubmed/30070631
http://dx.doi.org/10.7554/eLife.38111
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author Bertolin, Giulia
Bulteau, Anne-Laure
Alves-Guerra, Marie-Clotilde
Burel, Agnes
Lavault, Marie-Thérèse
Gavard, Olivia
Le Bras, Stephanie
Gagné, Jean-Philippe
Poirier, Guy G
Le Borgne, Roland
Prigent, Claude
Tramier, Marc
author_facet Bertolin, Giulia
Bulteau, Anne-Laure
Alves-Guerra, Marie-Clotilde
Burel, Agnes
Lavault, Marie-Thérèse
Gavard, Olivia
Le Bras, Stephanie
Gagné, Jean-Philippe
Poirier, Guy G
Le Borgne, Roland
Prigent, Claude
Tramier, Marc
author_sort Bertolin, Giulia
collection PubMed
description 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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spelling pubmed-61407142018-09-19 Aurora kinase A localises to mitochondria to control organelle dynamics and energy production Bertolin, Giulia Bulteau, Anne-Laure Alves-Guerra, Marie-Clotilde Burel, Agnes Lavault, Marie-Thérèse Gavard, Olivia Le Bras, Stephanie Gagné, Jean-Philippe Poirier, Guy G Le Borgne, Roland Prigent, Claude Tramier, Marc eLife Cancer Biology 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. eLife Sciences Publications, Ltd 2018-08-02 /pmc/articles/PMC6140714/ /pubmed/30070631 http://dx.doi.org/10.7554/eLife.38111 Text en © 2018, Bertolin et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cancer Biology
Bertolin, Giulia
Bulteau, Anne-Laure
Alves-Guerra, Marie-Clotilde
Burel, Agnes
Lavault, Marie-Thérèse
Gavard, Olivia
Le Bras, Stephanie
Gagné, Jean-Philippe
Poirier, Guy G
Le Borgne, Roland
Prigent, Claude
Tramier, Marc
Aurora kinase A localises to mitochondria to control organelle dynamics and energy production
title Aurora kinase A localises to mitochondria to control organelle dynamics and energy production
title_full Aurora kinase A localises to mitochondria to control organelle dynamics and energy production
title_fullStr Aurora kinase A localises to mitochondria to control organelle dynamics and energy production
title_full_unstemmed Aurora kinase A localises to mitochondria to control organelle dynamics and energy production
title_short Aurora kinase A localises to mitochondria to control organelle dynamics and energy production
title_sort aurora kinase a localises to mitochondria to control organelle dynamics and energy production
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140714/
https://www.ncbi.nlm.nih.gov/pubmed/30070631
http://dx.doi.org/10.7554/eLife.38111
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