Constitutive regulation of mitochondrial morphology by Aurora A kinase depends on a predicted cryptic targeting sequence at the N-terminus.
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Date
2018-06-13ICR Author
Author
Grant, R
Abdelbaki, A
Bertoldi, A
Gavilan, MP
Mansfeld, J
Glover, DM
Lindon, C
Type
Journal Article
Metadata
Show full item recordAbstract
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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Subject
Cell Line
Cytoplasm
Mitochondria
Humans
Mitochondrial Proteins
Protein Kinase Inhibitors
Proteomics
Protein Binding
Aurora Kinase A
Research team
Post-translational modifications and cell proliferation
Language
eng
Date accepted
2018-05-18
License start date
2018-06
Citation
Open biology, 2018, 8 (6)
Publisher
ROYAL SOC