Constitutive regulation of mitochondrial morphology by Aurora A kinase depends on a predicted cryptic targeting sequence at the N-terminus.
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Embargo End Date
ICR Authors
Authors
Grant, R
Abdelbaki, A
Bertoldi, A
Gavilan, MP
Mansfeld, J
Glover, DM
Lindon, C
Abdelbaki, A
Bertoldi, A
Gavilan, MP
Mansfeld, J
Glover, DM
Lindon, C
Document Type
Journal Article
Date
2018-06-13
Date Accepted
2018-05-18
Abstract
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.
Citation
Open biology, 2018, 8 (6)
Source Title
Publisher
ROYAL SOC
ISSN
2046-2441
eISSN
2046-2441
Collections
Research Team
Post-translational modifications and cell proliferation