RT Journal Article
T1 Constitutive regulation of mitochondrial morphology by Aurora A kinase depends on a predicted cryptic targeting sequence at the N-terminus.
A1 Grant, Rhys
A1 Abdelbaki, Ahmed
A1 Bertoldi, Alessia
A1 Gavilan, Maria P
A1 Mansfeld, Jörg
A1 Glover, David M
A1 Lindon, Catherine
K1 AURKA
K1 mitochondria
K1 mitochondrial dynamics
AB 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.
YR 2018
FD 2018
LK http://hdl.handle.net/10668/12589
UL http://hdl.handle.net/10668/12589
LA en
DS RISalud
RD Apr 18, 2025