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Constitutive regulation of mitochondrial morphology by Aurora A kinase depends on a predicted cryptic targeting sequence at the N-terminus

Aurora A kinase (AURKA) is a major regulator of mitosis and an important driver of cancer progression. The roles of AURKA outside of mitosis, and how these might contribute to cancer progression, are not well understood. Here, we show that a fraction of cytoplasmic AURKA is associated with mitochond...

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Autores principales: Grant, Rhys, Abdelbaki, Ahmed, Bertoldi, Alessia, Gavilan, Maria P., Mansfeld, Jörg, Glover, David M., Lindon, Catherine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030116/
https://www.ncbi.nlm.nih.gov/pubmed/29899121
http://dx.doi.org/10.1098/rsob.170272
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author Grant, Rhys
Abdelbaki, Ahmed
Bertoldi, Alessia
Gavilan, Maria P.
Mansfeld, Jörg
Glover, David M.
Lindon, Catherine
author_facet Grant, Rhys
Abdelbaki, Ahmed
Bertoldi, Alessia
Gavilan, Maria P.
Mansfeld, Jörg
Glover, David M.
Lindon, Catherine
author_sort Grant, Rhys
collection PubMed
description Aurora A kinase (AURKA) is a major regulator of mitosis and an important driver of cancer progression. The roles of AURKA outside of mitosis, and how these might contribute to cancer progression, are not well understood. Here, we show that a fraction of cytoplasmic AURKA is associated with mitochondria, co-fractionating in cell extracts and interacting with mitochondrial proteins by reciprocal co-immunoprecipitation. We have also found that the dynamics of the mitochondrial network are sensitive to AURKA inhibition, depletion or overexpression. This can account for the different mitochondrial morphologies observed in RPE-1 and U2OS cell lines, which show very different levels of expression of AURKA. We identify the mitochondrial fraction of AURKA as influencing mitochondrial morphology, because an N-terminally truncated version of the kinase that does not localize to mitochondria does not affect the mitochondrial network. We identify a cryptic mitochondrial targeting sequence in the AURKA N-terminus and discuss how alternative conformations of the protein may influence its cytoplasmic fate.
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spelling pubmed-60301162018-07-17 Constitutive regulation of mitochondrial morphology by Aurora A kinase depends on a predicted cryptic targeting sequence at the N-terminus Grant, Rhys Abdelbaki, Ahmed Bertoldi, Alessia Gavilan, Maria P. Mansfeld, Jörg Glover, David M. Lindon, Catherine Open Biol Research Aurora A kinase (AURKA) is a major regulator of mitosis and an important driver of cancer progression. The roles of AURKA outside of mitosis, and how these might contribute to cancer progression, are not well understood. Here, we show that a fraction of cytoplasmic AURKA is associated with mitochondria, co-fractionating in cell extracts and interacting with mitochondrial proteins by reciprocal co-immunoprecipitation. We have also found that the dynamics of the mitochondrial network are sensitive to AURKA inhibition, depletion or overexpression. This can account for the different mitochondrial morphologies observed in RPE-1 and U2OS cell lines, which show very different levels of expression of AURKA. We identify the mitochondrial fraction of AURKA as influencing mitochondrial morphology, because an N-terminally truncated version of the kinase that does not localize to mitochondria does not affect the mitochondrial network. We identify a cryptic mitochondrial targeting sequence in the AURKA N-terminus and discuss how alternative conformations of the protein may influence its cytoplasmic fate. The Royal Society 2018-06-13 /pmc/articles/PMC6030116/ /pubmed/29899121 http://dx.doi.org/10.1098/rsob.170272 Text en © 2018 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Research
Grant, Rhys
Abdelbaki, Ahmed
Bertoldi, Alessia
Gavilan, Maria P.
Mansfeld, Jörg
Glover, David M.
Lindon, Catherine
Constitutive regulation of mitochondrial morphology by Aurora A kinase depends on a predicted cryptic targeting sequence at the N-terminus
title Constitutive regulation of mitochondrial morphology by Aurora A kinase depends on a predicted cryptic targeting sequence at the N-terminus
title_full Constitutive regulation of mitochondrial morphology by Aurora A kinase depends on a predicted cryptic targeting sequence at the N-terminus
title_fullStr Constitutive regulation of mitochondrial morphology by Aurora A kinase depends on a predicted cryptic targeting sequence at the N-terminus
title_full_unstemmed Constitutive regulation of mitochondrial morphology by Aurora A kinase depends on a predicted cryptic targeting sequence at the N-terminus
title_short Constitutive regulation of mitochondrial morphology by Aurora A kinase depends on a predicted cryptic targeting sequence at the N-terminus
title_sort constitutive regulation of mitochondrial morphology by aurora a kinase depends on a predicted cryptic targeting sequence at the n-terminus
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030116/
https://www.ncbi.nlm.nih.gov/pubmed/29899121
http://dx.doi.org/10.1098/rsob.170272
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