Regulation of mitochondrial dynamics by Aurora A kinase

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 RPE1 and U2OS cell lines, which show very different levels of expression of AURKA. We identify the mitochondrial fraction of AURKA as influencing mitochondrial morphology, since 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.peer-reviewed)

Aurora kinase A/AURKA interacts with the mitochondrial ATP synthase to regulate energy metabolism and cell death

“…Taken together, our data show for the first time that Complex V inhibition in breast cancer cells induces a cell cycle arrest in G0/G1 involving the cell cycle-related kinase AURKA. AURKA was previously found to act on mitochondrial functions (Bertolin et al, 2018;Grant et al, 2018;Bertolin et al, 2021), and we here provide evidence that the kinase can directly interact with the Complex V core subunits ATP5F1A and ATP5F1B. Altering AURKA, ATP5F1A or ATP5F1B levels induces dramatic metabolic changes which affect both the mitochondrial respiratory chain and glycolysis rates.…”

“…In conditions where the ATP synthase is pharmacologically inhibited, the levels of AURKA dramatically decrease and cells are arrested at G0/G1. Not only AURKA is a cell cycle protein with a clear mitochondrial localization and acting on mitochondrial functions at multiple levels (Bertolin et al, 2021(Bertolin et al, , 2018Grant et al, 2018), but it also mechanistically links cell cycle progression, Complex V functionality and the cellular metabolic capacity by interacting with Complex V subunits.…”

Aurora-A phosphorylates splicing factors and regulates alternative splicing

“…The enrichment analysis further revealed few highly-enriched biological processes related to mitochondrial functions (Figure 2A-B and Supplementary Figure S2A), a novel function of Aurora-A that was described recently (11,52,53). Accordingly, string-based protein-protein interaction network of the Aurora-A interactome clearly contains clusters of proteins (sub-networks) that correspond to mitochondrial functions (Supplementary Figure S2B).…”