UCP2 Regulates Embryonic Neurogenesis via ROS-Mediated Yap Alternation in the Developing Neocortex

Abstract

Abstract Mitochondrial metabolism is a fundamental process in tissue development. How this process play functions in embryonic neurogenesis remains largely unknown. Here, we show that mitochondrial uncoupling protein 2 (UCP2) regulates the embryonic neurogenesis by inhibiting the production of reactive oxygen species (ROS), which affect the proliferation of progenitors. In the embryonic brains of UCP2 knockdown or condition knockout mice, the proliferation of progenitors is significantly increased, while the differentiation of progenitors is reduced. Furthermore, we identify that Yap is the response protein of UCP2-mediated ROS production. When UCP2 is inactive, the production of ROS is increased. The amount of Yap protein is increased as Yap degradation through ubiquitin–proteasome proteolytic pathway is decreased. The defect caused by UCP2 depression can be rescued by Yap downregulation. Collectively, our results demonstrate that UCP2 regulates embryonic neurogenesis through ROS-mediated Yap alternation, thus shedding new sight on mitochondrial metabolism involved in embryonic neurogenesis.