| First Author | Kastl L | Year | 2014 |
| Journal | FEBS Lett | Volume | 588 |
| Issue | 1 | Pages | 175-83 |
| PubMed ID | 24316229 | Mgi Jnum | J:206308 |
| Mgi Id | MGI:5550010 | Doi | 10.1016/j.febslet.2013.11.033 |
| Citation | Kastl L, et al. (2014) TNF-alpha mediates mitochondrial uncoupling and enhances ROS-dependent cell migration via NF-kappaB activation in liver cells. FEBS Lett 588(1):175-83 |
| abstractText | Development of hepatocellular carcinoma (HCC) is accompanied by a continuous increase in reactive oxygen species (ROS) levels. To investigate the primary source of ROS in liver cells, we used tumor necrosis factor-alpha (TNF-alpha) as stimulus. Applying inhibitors against the respiratory chain complexes, we identified mitochondria as primary source of ROS production. TNF-alpha altered mitochondrial integrity by mimicking a mild uncoupling effect in liver cells, as indicated by a 40% reduction in membrane potential and ATP depletion (35%). TNF-alpha-induced ROS production activated NF-kappaB 3.5-fold and subsequently enhanced migration up to 12.7-fold. This study identifies complex I and complex III of the mitochondrial respiratory chain as point of release of ROS upon TNF-alpha stimulation of liver cells, which enhances cell migration by activating NF-kappaB signalling. |
