Mitochondrial complex III ROS regulate adipocyte differentiation. Cell Metab 2011 Oct 05;14(4):537-44
Date
10/11/2011Pubmed ID
21982713Pubmed Central ID
PMC3190168DOI
10.1016/j.cmet.2011.08.007Scopus ID
2-s2.0-80053904684 (requires institutional sign-in at Scopus site) 570 CitationsAbstract
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.
Author List
Tormos KV, Anso E, Hamanaka RB, Eisenbart J, Joseph J, Kalyanaraman B, Chandel NSAuthor
Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdipocytesAntioxidants
CCAAT-Enhancer-Binding Proteins
Cell Differentiation
Electron Transport Complex III
Humans
Hydrogen Peroxide
Mechanistic Target of Rapamycin Complex 1
Mitochondria
Multiprotein Complexes
PPAR gamma
Proteins
Reactive Oxygen Species
Signal Transduction
TOR Serine-Threonine Kinases