title: Mitochondrial complex III ROS regulate adipocyte differentiation.
abstract: 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.
authors: Division of Pulmonary and Critical Care, Department of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA.
authors: Kathryn V
authors: KV
authors: Tormos
authors: Elena
authors: E
authors: Anso
authors: Robert B
authors: RB
authors: Hamanaka
authors: James
authors: J
authors: Eisenbart
authors: Joy
authors: J
authors: Joseph
authors: Balaraman
authors: B
authors: Kalyanaraman
authors: Navdeep S
authors: NS
authors: Chandel
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D000975:Antioxidants / Q000494:pharmacology; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002454:Cell Differentiation; D014450:Electron Transport Complex III / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D000076222:Mechanistic Target of Rapamycin Complex 1; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008928:Mitochondria / Q000378:metabolism; D046912:Multiprotein Complexes; D047495:PPAR gamma / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
chemical_list: D000975:Antioxidants; D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D046912:Multiprotein Complexes; D047495:PPAR gamma; D011506:Proteins; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D014450:Electron Transport Complex III