Nonetheless, the precise mechanism of action behind the acetaldehyde-induced unfavorable myocardial functional and morphological changes following either acute or chronic ethanol exposure remains elusive. Given that apoptosis and mitochondrial Tubeimoside-I damage are commonly present in response to ethanol challenge and are thought to play an essential role in alcoholism-elicited organ damage and complications, our current study was designed to address the role of mitochondrial function and apoptosis in ethanol-induced myocardial dysfunction. Here we took advantage of the novel transgenic mouse model generated in our labs with the cardiac-specific overexpression of alcohol dehydrogenase, which mimics an ����acetaldehyde overloaded���� model of alcoholic cardiomyopathy. Myocardial mitochondrial damage was assessed using mitochondrial superoxide accumulation and mitochondrial membrane potential. Mitochondria are known to play a key role in the maintenance of cardiac function and morphology through regulation of reactive oxygen species production and apoptosis. Mitochondria are often themselves targets of oxidative stress and contribute to mechanisms by which oxidative stress-related cell signals control cardiac contractile function. We further examined the roles of the two main apoptotic domains including one through activated death receptors in the cell surface and another via signals originated within the cell involving mitochondria as either an initiator or a magnifier. The death receptor pathway is usually triggered by the linkage of specific ligands to membrane receptors including tumor necrosis factor a and Fas receptor. To this end, expression of TNF-a, Fas, Fas ligand, Caspase8 and pro-caspase-8 was examined in wild-type FVB and ADH hearts following acute ethanol challenge. To monitor the change in mitochondrial death domain, cytosolic accumulation of procaspase-9, cytochrome C and apoptosis Tenacissoside-H inducing factor was examined. TUNEL assay and levels of the pro-apoptotic proteins Bax and Caspase-3 as well as the anti-apoptotic protein Bcl-2 were used as for overall assessment of apoptosis.