Ca2+-Induced Mitochondrial ROS Regulate the Early Embryonic Cell Cycle

Yue Han,Shoko Ishibashi,Javier Iglesias-Gonzalez,Yaoyao Chen,Nick R Love,Enrique Amaya

doi:10.1016/j.celrep.2017.12.042

Yue Han, Shoko Ishibashi + Show 4 more

Open Access

https://doi.org/10.1016/j.celrep.2017.12.042

Copy DOI

Abstract

SummaryWhile it is appreciated that reactive oxygen species (ROS) can act as second messengers in both homeostastic and stress response signaling pathways, potential roles for ROS during early vertebrate development have remained largely unexplored. Here, we show that fertilization in Xenopus embryos triggers a rapid increase in ROS levels, which oscillate with each cell division. Furthermore, we show that the fertilization-induced Ca2+ wave is necessary and sufficient to induce ROS production in activated or fertilized eggs. Using chemical inhibitors, we identified mitochondria as the major source of fertilization-induced ROS production. Inhibition of mitochondrial ROS production in early embryos results in cell-cycle arrest, in part, via ROS-dependent regulation of Cdc25C activity. This study reveals a role for oscillating ROS levels in early cell cycle regulation in Xenopus embryos.

Highlights

Reactive oxygen species (ROS), including the superoxide anion (O2dÀ), hydroxyl radical (OHdÀ), hydrogen peroxide (H2O2), and singlet oxygen (1O2), have various functions in cells and tissues
We show that Ca2+ induces ROS production after fertilization and that the major sources of ROS during the early embryonic development are the mitochondria
We show that mitochondrial ROS (mtROS) production oscillates with the cell cycle and this oscillation participates in the regulation of the cell cycle in early Xenopus embryos, at least partly through ROS-mediated modulation of the cell cycle phosphatase Cdc25C

Summary

Graphical Abstract

Han et al show that the fertilizationtriggered calcium wave induces reactive oxygen species production from mitochondria, which oscillate with each cell division in Xenopus embryos. They demonstrate that inhibition of mitochondrial ROS production disrupts cell cycle progression. Highlights d ROS, including hydrogen peroxide, are produced after fertilization in Xenopus d Ca2+ signaling after fertilization induces ROS production in mitochondria d Mitochondria are the major source of oscillating ROS levels d ROS regulate Cdc25C activity and the early cell cycle. 2018, Cell Reports 22, 218–231 January 2, 2018 a 2017 The Authors.

SUMMARY

INTRODUCTION

RESULTS

Findings

DISCUSSION

EXPERIMENTAL PROCEDURES