Oxidative stress induces mitotic arrest by inhibiting Aurora A-involved mitotic spindle formation

Publication date: Available online 23 December 2016
Source:Free Radical Biology and Medicine
Author(s): Guang-Fei Wang, Qincai Dong, Yuanyuan Bai, Jing Yuan, Quanbin Xu, Cheng Cao, Xuan Liu
Oxidative stress contributes to the oxidative modification of cellular components, including lipids, proteins and DNA, and results in DNA damage, cell cycle arrest, cellular dysfunction and apoptosis. However, the mechanism underlying oxidative stress-induced mitotic abnormalities is not fully understood. In this study, we demonstrated that exogenous and endogenous reactive oxygen species (ROS) promoted mitotic arrest. Delayed formation and abnormal function of the mitotic spindle, which directly impeded mitosis and promoted abnormal chromosome separation, was responsible for ROS-induced mitotic arrest. As a key regulator of mitotic spindle assembly, Aurora A kinase was hyperphosphorylated in early mitosis under oxidative stress, which may disturb the function of Aurora A in mitotic spindle formation. Our findings identified a mechanism by which ROS regulate mitotic progression and indicated a potential molecular target for the treatment of oxidative stress-related diseases.

Graphical abstract

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