Enhanced O2N2 and oxidative Khasianine stress are known to induce hypertrophy in cardiomyocytes. As the major metabolite of ethanol, acetaldehyde enhances free radical generation through aldehyde oxidase and xanthine oxidaseassociated oxidation, leading to accumulation of O2N2 as shown in our present study. Our earlier report indicated that ADH produced greater levels of lipid peroxidation and protein carbonyls in hearts from the alcohol-fed mice, indicating a key role of free radical formation in alcohol- and acetaldehydeinduced cardiac damage. To the contrary, the occurrence of apoptosis contributes to the loss of cardiomyocytes, which is deemed as a predictor of adverse outcomes for cardiac diseases and eventually heart failure. With the concurrent hypertrophy and loss of cell number in cardiomyocytes, it is not surprising to find the unchanged gross heart weight in response to acute ethanol exposure. Mitochondrial Eupalinilide-C integrity plays a pivotal role for cell survival and function. Loss of mitochondrial integrity leads to the development of several diseases such as neurodegenerative disorders, diabetes and ischemia reperfusion-induced heart damage. Recently, mitochondrial dysfunction also received some attentions in the onset of alcoholic complications. Data from our current study revealed elevated mitochondrial O2N2 production and reduced mitochondrial membrane potential in hearts following acute ethanol exposure. More intriguingly, the ethanol-induced changes in mitochondrial membrane potential and mitochondrial O2N2 production were exaggerated by the ADH transgene. These observations were in line with the changes in myocardial contractility and histology in both FVB and ADH mice following ethanol exposure, suggesting the essential role of mitochondria in ADH-induced exacerbation of myocardial injury in response to ethanol exposure. Mitochondrial damage has been demonstrated to result in apoptosis through mitochondrial pathways. Apoptosis or programmed cell death plays a key role in the pathogenesis of a variety of diseases including atherosclerosis, myocardial ischemia and reperfusion injury, diabetic cardiomyopathy and alcoholic cardiomyopathy.