Mitochondrial Complex III ROS Regulate Adipocyte Differentiation

Division of Pulmonary and Critical Care, Department of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA.
Cell metabolism (Impact Factor: 17.57). 10/2011; 14(4):537-44. DOI: 10.1016/j.cmet.2011.08.007
Source: PubMed


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 reactive oxygen species (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 that 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.

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Available from: Robert B Hamanaka, Jan 08, 2014
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    • "Higher endogenous and uncoupled oxygen consumption is also observed after the adipogenic differentiation in hMSCs and in Simpson-Golabi-Behmel syndrome subcutaneous preadipocytes (Keuper et al., 2014; Zhang et al., 2013). Mitochondrial biogenesis is increased through adipogenic differentiation of hMSCs (Tormos et al., 2011; Zhang et al., 2013). Mitochondria of adipocytes are preferentially distributed around the lipid droplets. "
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    • "DNA-binding activity, which is required for the terminal differentiation of an adipocyte (Lee et al., 2009; Tormos et al., 2011). Our results showed that Chemerin remarkably increases the expression of adipogenic genes PPARg, C/EBPa and UCP1, and intracellular ROS levels. "
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