Abstract
Reactive oxygen species (ROS), superoxide anion and hydrogen peroxide, are generated as byproducts of oxidative phosphorylation in the mitochondria or via cell signaling-induced NADPH oxidases in the cytosol. In the recent two decades, a plethora of studies established that elevated ROS levels generated by oxidative eustress are crucial physiological mediators of many cellular and developmental processes. In this review, we discuss the mechanisms of ROS generation and regulation, current understanding of ROS functions in the maintenance of adult and embryonic stem cells, as well as in the process of cell reprogramming to a pluripotent state. Recently discovered cell-non-autonomous ROS functions mediated by growth factors are crucial for controlling cell differentiation and cellular immune response in Drosophila. Importantly, many physiological functions of ROS discovered in Drosophila may allow for deciphering and understanding analogous processes in human, which could potentially lead to the development of novel therapeutic approaches in ROS-associated diseases treatment.
Highlights
Reactive oxygen species (ROS) represents a group of molecules derived from oxygen, which are formed by reduction/oxidation reactions or by electronic excitation
The superoxide anion radical (O2.−) and hydrogen peroxide (H2O2) are key ROS signaling agents generated by the mitochondrial electron transport chain and by more than 40 enzymes, mainly NADPH oxidases, that are regulated by growth factors and cytokines
Eleven different sites of electron leak resulting in superoxide anion/ROS generation have been shown in the electron transport chain (ETC) of isolated mitochondria (Brand, 2016)
Summary
Reactive oxygen species (ROS) represents a group of molecules derived from oxygen, which are formed by reduction/oxidation reactions (redox reactions) or by electronic excitation. H2O2 is the major oxidant having pleiotropic signaling functions via specific reversible oxidation of protein targets. The H2O2 regulates various signal transduction events, cell metabolism, and stress responses, ROS Functions in Stem Cells being involved in numerous cellular and developmental processes (Jones and Sies, 2015). We discuss the physiological functions of intracellular ROS, both as a redox signal and a secondary messenger of various cell signaling pathways, in the context of regulation of stem cell self-renewal and differentiation during various developmental processes in Drosophila and mammals. The sources and regulation of intracellular ROS, as well as their downstream molecular targets and important functions in embryonic stem cells, nuclear reprogramming to pluripotent state, and ROSmediated cell-non-autonomous signaling are discussed. Other aspects of ROS signaling and their biological functions have been discussed in a number of excellent reviews (Bigarella et al, 2014; Holmstrom and Finkel, 2014; Sies and Jones, 2020)
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