Mitochondrial complex III ROS regulate adipocyte differentiation

By K. Tormos, Elena Ansó, R. Hamanaka, J. Eisenbart, J. Joseph, B. Kalyanaraman, Navdeep S. Chandel. Cell Metabolism, 2011

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SUMMARY Adipocyte differentiation is characterized by an increase in mitochondrial metabolism. However it is not known whether the increase in mitochondrial metabolism is essential for differentiation or a byproduct of the differentiation process. Here, we report that primary human mesenchymal stem cells undergoing differentiation into adipocytes display an early increase in mitochondrial metabolism, biogenesis, and ROS generation. This early increase in mitochondrial metabolism and ROS generation was dependent on mTORC1 signaling. Mitochondrial targeted antioxidants inhibited adipocyte differentiation which was rescued by the addition of exogenous hydrogen peroxide. Genetic manipulation of mitochondrial complex III revealed ROS generated from this complex is required to initiate adipocyte differentiation. These results indicate that mitochondrial metabolism and ROS generation are not simply a consequence of differentiation, but are a causal factor in promoting adipocyte differentiation.

Subfields: Cancer Research, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/613f365484f431a31a73e33c87bffdf5f7df2007

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In Molecular Biology

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Citations in the corpus

• Mitochondrial ROS signaling in organismal homeostasis. (2015, background): “…including wound healing (Xu and Chisholm, 2014), survival under hypoxia (Schieber and Chandel, 2014), intracellular pH homeostasis (Johnson et al., 2012), cell differentiation (Hamanaka and Chandel, 2010; Hamanaka et al., 2013; Tormos et al., 2011), and innate immunity (West et al., 2011).”
• Fate decision of mesenchymal stem cells: adipocytes or osteoblasts? (2016, background): “complex III is essential for the activation of adipogenic transcription factors.(130) These results implicate that the”
• Metabolic Plasticity in Stem Cell Homeostasis and Differentiation (2012, neutral): “…capacity is reduced and glycolysis-dependent anabolic pathways are enriched in stem cells including ESCs (Cho et al., 2006; Chung et al., 2007; Folmes et al., 2011a; Kondoh et al., 2007), long-term HSCs (Simsek et al., 2010), MSCs (Chen et al., 2008b), and hepatic stem cells (Turner et al., 2008).”
• Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling (2013, neutral): “We and others have shown that mitochondrial ROS (mROS), particularly complex III ROS, can function as signaling intermediates (Byun et al., 2008; Schieke et al., 2008; Tormos et al., 2011; Weinberg et al., 2010).”
• Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. (2014, background): “What we have learned is that ROS originating from mitochondrial rather than from other intracellular sources, when they exceed the homeostatic level, are among the most pathogenic factors (222, 382, 383, 437, 467).”