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...
Main Authors: | , , , , , , , , , , , |
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Language: | English |
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eLife Sciences Publications Ltd
2018-08-01
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Series: | eLife |
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Online Access: | https://elifesciences.org/articles/38111 |
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author | Giulia Bertolin Anne-Laure Bulteau Marie-Clotilde Alves-Guerra Agnes Burel Marie-Thérèse Lavault Olivia Gavard Stephanie Le Bras Jean-Philippe Gagné Guy G Poirier Roland Le Borgne Claude Prigent Marc Tramier |
author_facet | Giulia Bertolin Anne-Laure Bulteau Marie-Clotilde Alves-Guerra Agnes Burel Marie-Thérèse Lavault Olivia Gavard Stephanie Le Bras Jean-Philippe Gagné Guy G Poirier Roland Le Borgne Claude Prigent Marc Tramier |
author_sort | Giulia Bertolin |
collection | DOAJ |
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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format | Article |
id | doaj.art-c41a0e3730934372b8b560ab43eb1bed |
institution | Directory Open Access Journal |
issn | 2050-084X |
language | English |
last_indexed | 2024-04-12T01:47:34Z |
publishDate | 2018-08-01 |
publisher | eLife Sciences Publications Ltd |
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series | eLife |
spelling | doaj.art-c41a0e3730934372b8b560ab43eb1bed2022-12-22T03:53:02ZengeLife Sciences Publications LtdeLife2050-084X2018-08-01710.7554/eLife.38111Aurora kinase A localises to mitochondria to control organelle dynamics and energy productionGiulia Bertolin0https://orcid.org/0000-0002-7359-5733Anne-Laure Bulteau1Marie-Clotilde Alves-Guerra2Agnes Burel3Marie-Thérèse Lavault4Olivia Gavard5Stephanie Le Bras6Jean-Philippe Gagné7Guy G Poirier8Roland Le Borgne9https://orcid.org/0000-0001-6892-278XClaude Prigent10https://orcid.org/0000-0001-8515-8699Marc Tramier11https://orcid.org/0000-0001-8200-6446CNRS, UMR 6290, Rennes, France; Université de Rennes 1, UBL, Genetics and Development Institute of Rennes (IGDR), Rennes, FranceENS de Lyon, Lyon, France; CNRS UMR 5242, Lyon, France; INRA USC 1370, Lyon, FranceInserm, U1016, Institut Cochin, Paris, France; CNRS, UMR 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, FranceMicroscopy Rennes Imaging Centre, SFR Biosit, UMS CNRS 3480- US INSERM 018, Université de Rennes, Rennes, FranceMicroscopy Rennes Imaging Centre, SFR Biosit, UMS CNRS 3480- US INSERM 018, Université de Rennes, Rennes, FranceCNRS, UMR 6290, Rennes, France; Université de Rennes 1, UBL, Genetics and Development Institute of Rennes (IGDR), Rennes, France; Equipes labélisées Ligue Contre Le Cancer, Rennes, France; Centre de recherche du CHU de Québec, Faculté de Médecine, Université Laval, Québec, CanadaCNRS, UMR 6290, Rennes, France; Université de Rennes 1, UBL, Genetics and Development Institute of Rennes (IGDR), Rennes, FranceCentre de recherche du CHU de Québec, Faculté de Médecine, Université Laval, Québec, CanadaCentre de recherche du CHU de Québec, Faculté de Médecine, Université Laval, Québec, CanadaCNRS, UMR 6290, Rennes, France; Université de Rennes 1, UBL, Genetics and Development Institute of Rennes (IGDR), Rennes, France; Equipes labélisées Ligue Contre Le Cancer, Rennes, FranceCNRS, UMR 6290, Rennes, France; Université de Rennes 1, UBL, Genetics and Development Institute of Rennes (IGDR), Rennes, France; Equipes labélisées Ligue Contre Le Cancer, Rennes, FranceCNRS, UMR 6290, Rennes, France; Université de Rennes 1, UBL, Genetics and Development Institute of Rennes (IGDR), Rennes, France; Microscopy Rennes Imaging Centre, SFR Biosit, UMS CNRS 3480- US INSERM 018, Université de Rennes, Rennes, FranceMany 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.https://elifesciences.org/articles/38111mitochondriacell cycleepithelial cancer |
spellingShingle | Giulia Bertolin Anne-Laure Bulteau Marie-Clotilde Alves-Guerra Agnes Burel Marie-Thérèse Lavault Olivia Gavard Stephanie Le Bras Jean-Philippe Gagné Guy G Poirier Roland Le Borgne Claude Prigent Marc Tramier Aurora kinase A localises to mitochondria to control organelle dynamics and energy production eLife mitochondria cell cycle epithelial cancer |
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 | mitochondria cell cycle epithelial cancer |
url | https://elifesciences.org/articles/38111 |
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