Control of the pericentrosomal H2O2 level by peroxiredoxin I is critical for mitotic progression.
Bottom Line: The intracellular concentration of H2O2 increases as the cell cycle progresses.Whereas the centrosome is shielded from H2O2 through its association with the H2O2-eliminating enzyme peroxiredoxin I (PrxI) during interphase, the centrosome-associated PrxI is selectively inactivated through phosphorylation by Cdk1 during early mitosis, thereby exposing the centrosome to H2O2 and facilitating inactivation of centrosome-bound phosphatases.Dephosphorylation of PrxI by okadaic acid-sensitive phosphatases during late mitosis again shields the centrosome from H2O2 and thereby allows the reactivation of Cdk1-opposing phosphatases at the organelle.
Affiliation: Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, South Korea.Show MeSH
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Mentions: Reactive oxygen species including H2O2 increase gradually during cell cycle progression. There are multiple potential sources of H2O2 during mitosis, which include NADPH oxidase 4 (Yamaura et al., 2009) and arachidonic acid metabolism coupled to cPLA2 (cytosolic phospholipase A2; van Rossum et al., 2001; Cho et al., 2011). Indeed, we found that diphenyleneiodonium (DPI; NADPH oxidase inhibitor), AACOCF3 (cPLA2 inhibitor) and methyl arachidonyl fluorophosphonate (MAFP; cPLA2 inhibitor), and nordihydroguaiaretic acid (NDGA; lipoxygenase inhibitor) each attenuated mitotic entry in HeLa cells (Fig. 3, A–D). NADPH oxidase 4 and cPLA2 are localized to the membranes of ER, which accumulates around the centrosome before nuclear breakdown (Whitaker, 2006; Lassègue et al., 2012). It is therefore possible that sources of H2O2 are arranged specifically to channel H2O2 to the centrosome in mitotic cells.
Affiliation: Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, South Korea.