Eukaryotic cells must possess mechanisms for condensing and decondensing chromatin. Chromatin condensation is particularly evident during mitosis and cell death induced by apoptosis, whereas chromatin decondensation is necessary for replication, repair, recombination and transcription. Histones are among the numerous DNA-binding proteins that control the level of DNA condensation, and post-translational modification of histone tails plays a critical role in the dynamic condensation/decondensation that occurs during the cell cycle. Phosphorylation of Ser10 in the tails of histone H3 has been extensively studied in many organisms. Interestingly, this modification is involved in both transcription and cell division, two events requiring opposite alterations in the degree of chromatin compaction. How does one and the same modification of histone H3 fulfil such roles? For instance, in interphase, phosphorylation of H3 correlates with chromatin relaxation and gene expression, whereas in mitosis it correlates with chromosome condensation. What is the kinase and under what circumstances does Ser10 becomes phosphorylated? Most importantly, what are the consequences of phosphorylation of this residue?

We have previously reported on the cloning of XlEg5, a Xenopus laevis kinesin-related protein from thebimC family (Le Guellec, R., Paris, J., Couturier, A., Roghi, C., and Philippe, M. (1991) Mol. Cell. Biol. 11, 3395–3408) as well as pEg2, an Aurora-related serine/threonine kinase (Roghi, C., Giet, R., Uzbekov, R., Morin, N., Chartrain, I., Le Guellec, R., Couturier, A., Dorée, M., Philippe, M., and Prigent, C. (1998) J. Cell Sci. 111, 557–572). Inhibition of either XlEg5 or pEg2 activity during mitosis in Xenopus egg extract led to monopolar spindle formation. Here, we report that inXenopus XL2 cells, pEg2 and XlEg5 are both confined to separated centrosomes in prophase, and then to the microtubule spindle poles. We also show that pEg2 co-immunoprecipitates with XlEg5 from egg extracts and XL2 cell lysates. Both proteins can directly interactin vitro, but also through the two-hybrid system. Furthermore immunoprecipitated pEg2 were found to remain active when bound to the beads and phosphorylate XlEg5 present in the precipitate. Two-dimensional mapping of XlEg5 tryptic peptides phosphorylatedin vivo first confirmed that XlEg5 was phosphorylated by p34^cdc2 and next revealed that in vitro pEg2 kinase phosphorylated XlEg5 on the same stalk domain serine residue that was phosphorylated in metabolically labeled XL2 cells. The kinesin-related XlEg5 is to our knowledge the first in vivo substrate ever reported for an Aurora-related kinase.

Many epithelial cancers show cell cycle dysfunction tightly correlated with the overexpression of the serine/threonine kinase Aurora A (AURKA). Its role in mitotic progression has been extensively characterised, and evidence for new AURKA functions emerges. Here, we reveal that AURKA is located and imported in mitochondria in several human cancer cell lines. Mitochondrial AURKA impacts on two organelle functions: mitochondrial dynamics and energy production. When AURKA is expressed at endogenous levels during interphase, it induces mitochondrial fragmentation independently from RALA. Conversely, AURKA enhances mitochondrial fusion and ATP production when it is over-expressed. We demonstrate that AURKA directly regulates mitochondrial functions and that AURKA over-expression promotes metabolic reprogramming by increasing mitochondrial interconnectivity. Our work paves the way to anti-cancer therapeutics based on the simultaneous targeting of mitochondrial functions and AURKA inhibition.

All living organisms on Earth are made up of cells, which are the functional unit of life. Eukaryotic organisms can consist of a single cell (unicellular) or a group of either identical or different cells (multicellular). Biologists have always been fascinated by how a single cell, such as an egg, can give rise to an entire organism, such as the human body, composed of billions of cells, including hundreds of different cell types. This is made possible by cell division, whereby a single cell divides to form two cells. During a symmetric cell division, a mother cell produces two daughter cells, while an asymmetric cell division results in a mother and a daughter cell that have different fates (different morphologies, cellular compositions, replicative potentials, and/or capacities to differentiate). In biology, the cell cycle refers to the sequence of events that a cell must go through in order to divide. These events, which always occur in the same order, define the different stages of the cell cycle: G1, S, G2, and M. What is fascinating about the cell cycle is its universality, and the main reason for this is that the genetic information of the cell is encoded by exactly the same molecular entity with exactly the same structure: the DNA double helix. Since both daughter cells always inherit their genetic information from their parent cell, the underlying fundamentals of the cell cycle—DNA replication and chromosome segregation—are shared by all organisms. This review goes back in time to provide a historical summary of the main discoveries that led to the current understanding of how cells divide and how cell division is regulated to remain highly reproducible.