Dual Mode of Mitochondrial ROS Action during Reprogramming to Pluripotency

• Published in: International journal of molecular sciences Vol. 23; no. 18; p. 10924
• Main Authors: Skvortsova, Elena V., Nazarov, Igor B., Tomilin, Alexey N., Sinenko, Sergey A.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 18.09.2022; MDPI
• Subjects: Adenosine triphosphate; Cell cycle; Cloning; complex I (CI) of electron transport chain (ETC); Electron transport; Electron transport chain; Embryo fibroblasts; induced pluripotent stem cells (iPSCs); Inhibitory postsynaptic potentials; Metabolism; Mitochondria; NADH-ubiquinone oxidoreductase; Ndufb10; Ndufs1; Oxidative phosphorylation; Phosphorylation; Physiology; Pluripotency; reactive oxygen species (ROS); Rotenone; Scavenging; Somatic cells; Stem cell transplantation; Stem cells; Ubiquinone oxidoreductase
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms231810924

Essential changes in cell metabolism and redox signaling occur during the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). In this paper, using genetic and pharmacological approaches, we have investigated the role of electron transport chain (ETC) complex-I (CI) of mitochondria in the process of cell reprogramming to pluripotency. Knockdown of NADH-ubiquinone oxidoreductase core subunits S1 (Ndufs1) or subunit B10 (Ndufb10) of the CI or inhibition of this complex with rotenone during mouse embryonic fibroblast (MEF) reprogramming resulted in a significantly decreased number of induced pluripotent stem cells (iPSCs). We have found that mitochondria and ROS levels due course of the reprogramming tightly correlate with each other, both reaching peak by day 3 and significantly declining by day 10 of the process. The transient augmentation of mitochondrial reactive oxygen species (ROS) could be attenuated by antioxidant treatment, which ameliorated overall reprogramming. However, ROS scavenging after day 3 or during the entire course of reprogramming was suppressive for iPSC formation. The ROS scavenging within the CI-deficient iPSC-precursors did not improve, but further suppressed the reprogramming. Our data therefore point to distinct modes of mitochondrial ROS action during the early versus mid and late stages of reprogramming. The data further substantiate the paradigm that balanced levels of oxidative phosphorylation have to be maintained on the route to pluripotency.