Our laboratory is interested in studying the biochemical mechanisms by which alcoholic beverages produce liver damage. It is known that alcohol liver damage is associated with an impairment of the function of mitochondria, which is the powerhouse of the cell. In liver cells, alcohol interacts with a protein called cytochrome P450 2E1 (CYP2E1), the result of this interaction being an increased rate of oxidation of alcohol to acetaldehyde and toxic substances called free radicals. Our main hypothesis is that CYP2E1-derived free radicals react specifically with mitochondrial DNA, triggering mitochondrial damage and cell death. Molecules that specifically protect mitochondrial DNA from free radicals therefore could be a new therapeutic approach against alcoholic liver disease. To evaluate our hypothesis, we use cell fractions (endoplasmic reticulum, mitochondria), cells (liver cells in culture) and experimental animals (mice), and analytical, biological and cellular chemistry techniques including HPLC, polarography, real time PCR, RT-PCR, ELISA, western blot, chemiluminescence, fluorimetry, spectrophotometry, flow cytometry, and fluorescence microscopy.