| First Author | Yoon JC | Year | 2010 |
| Journal | Genes Dev | Volume | 24 |
| Issue | 14 | Pages | 1507-18 |
| PubMed ID | 20634317 | Mgi Jnum | J:161769 |
| Mgi Id | MGI:4461325 | Doi | 10.1101/gad.1924910 |
| Citation | Yoon JC, et al. (2010) Wnt signaling regulates mitochondrial physiology and insulin sensitivity. Genes Dev 24(14):1507-18 |
| abstractText | Mitochondria serve a critical role in physiology and disease. The genetic basis of mitochondrial regulation in mammalian cells has not yet been detailed. We performed a large-scale RNAi screen to systematically identify genes that affect mitochondrial abundance and function. This screen revealed previously unrecognized roles for >150 proteins in mitochondrial regulation. We report that increased Wnt signals are a potent activator of mitochondrial biogenesis and reactive oxygen species (ROS) generation, leading to DNA damage and acceleration of cellular senescence in primary cells. The signaling protein insulin receptor substrate-1 (IRS-1), shown here to be a transcriptional target of Wnt, is induced in this setting. The increased level of IRS-1 drives activation of mitochondrial biogenesis; furthermore, in insulin-responsive cell types, it enhances insulin signaling, raising the possibility that Wnt proteins may be used to modulate glucose homeostasis. Our results identify a key component of the mitochondrial regulatory apparatus with a potentially important link to metabolic and degenerative disorders. |
