Int J Stem Cells.  2015 May;8(1):24-35. 10.15283/ijsc.2015.8.1.24.

Regulation of Stem Cell Fate by ROS-mediated Alteration of Metabolism

• Ryu JM
• Lee HJ
• Jung YH
• Lee KH
• Kim DI
• Kim JY
• Ko SH
• Choi GE
• Chai II
• Song EJ
• Oh JY
• Lee SJ
• Han HJ

• KMID: 2380796
• DOI: http://doi.org/10.15283/ijsc.2015.8.1.24

Abstract

Stem cells have attracted much attention due to their distinct features that support infinite self-renewal and differentiation into the cellular derivatives of three lineages. Recent studies have suggested that many stem cells both embryonic and adult stem cells reside in a specialized niche defined by hypoxic condition. In this respect, distinguishing functional differences arising from the oxygen concentration is important in understanding the nature of stem cells and in controlling stem cell fate for therapeutic purposes. ROS act as cellular signaling molecules involved in the propagation of signaling and the translation of environmental cues into cellular responses to maintain cellular homeostasis, which is mediated by the coordination of various cellular processes, and to adapt cellular activity to available bioenergetic sources. Thus, in this review, we describe the physiological role of ROS in stem cell fate and its effect on the metabolic regulation of stem cells.

Keyword

Reactive oxygen species; Metabolism; Glucose; Amino acid; Fatty acid; Stem cell fate

MeSH Terms

Adult Stem Cells
Cues
Energy Metabolism
Glucose
Homeostasis
Metabolism*
Oxygen
Reactive Oxygen Species
Stem Cells*
Glucose
Oxygen
Reactive Oxygen Species

Figure

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  Fig. 1 ROS generation in cell. There are three different forms of intracellular ROS: superoxide anions (O2−), hydrogen peroxide (H2O2), and hydroxyl radicals (OH−). O2− can be produced by NADPH oxidase (NOX) and mitochondrial complex I & III, as well as physical stimuli such as UV and radiation, which subsequently catalyzed by SOD to H2O2, the most potent ROS [Modified from Bigarella et al. (122). Copyright 2014 by the Company of Biologists Ltd. Adapted with permission.].

• 

  Fig. 2 Role of ROS-induced HIF-1α in regulation of glycolytic metabolism. ROS stabilize HIF-1α by inhibition of ubiquitination and proteasomal degradation and accumulated HIF-1α promotes expression of glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), and pyruvate dehydrogenase kinase (PDK1). These glycolytic metabolism-related gene expressions elicit the metabolism flux shift from oxidative phosphorylation to glycolysis and subsequently regulate the stem cell fate.

• 

  Fig. 3 Crosstalk between ROS and Gln metabolism. ROS is involve in control of α-ketoglutarate (α-KG) and succinate ratio through regulation of the glutamine (Gln) metabolism, which catalyzed to glutamate (Glu) by glutaminase and resulted in increase of α-KG level. In addition, availability of Gln, Glu, and cysteine (Cys) are involved in maintenance of redox homeostasis through biosynthesis of cellular glutathione (GSH).

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  Fig. 4 Role of ROS in regulation of lipid metabolism. ROS increased HIF-1α along with sterol regulatory-element binding protein 1 (SREBP) and SREBP cleavage activating protein (SCAP1) expression. SREBP stimulates expression of lipogenic genes including the FAS gene. FAS stimulate lipogenesis with spending NADPH and resulted in increase of NADP+/NADPH ratio, which is involved in alteration of the redox balance and metabolic shift to compensate for the shortage of oxygen.

Reference

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