Repository logo
 

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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Grant, Rhys 
Abdelbaki, Ahmed 
Bertoldi, Alessia 
Gavilan, Maria P 

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.

Description

Keywords

AURKA, mitochondria, mitochondrial dynamics, Aurora Kinase A, Cell Line, Cytoplasm, Humans, Mitochondria, Mitochondrial Proteins, Protein Binding, Protein Kinase Inhibitors, Proteomics

Journal Title

Open Biol

Conference Name

Journal ISSN

2046-2441
2046-2441

Volume Title

8

Publisher

The Royal Society
Sponsorship
Medical Research Council (MR/M01102X/1)
MRC (982635)
Cancer Research UK (18795)
MRC CRUK