Beclin1 directly interacts not only with bcl-2 but also with other anti-apoptotic proteins of the bcl-2 family such as bcl-xL. Cardiac bcl-2 overexpression also inhibits autophagy in murine heart cells. This present study focuses on an understanding of the molecular mechanisms underlying DOX-induced cardiac toxicity. It identifies p53 as a candidate in augmenting retrograde signaling leading to cardiac injury by using genetic manipulations, functional tests, ultrastructural analyses, and biochemical assays. One approach to solving this problem is to rely on biochemical assays of oxidatively damaged products. A major problem with these assays, however, is that the oxidatively damaged products are susceptible to further in vitro oxidation, which hinders accurate measurement of levels of oxidatively damaged products in cellular organelles and in specific cell types from complex tissues. To circumvent this problem, the Oberley laboratory and others have developed techniques to localize and quantify oxidatively damaged products using specific antibodies coupled with electron microscopy procedures. Two previous studies have validated the immunomorphologic approaches presented herein by documenting good agreement between biochemical and immunomorphologic analyses in an experimental model of oxidative stress. We have previously shown that DOX causes significant oxidative damage manifested by increased levels of 4HNE adducted protein levels in mitochondria. Recent studies suggest that p53 plays an important role in maintaining Nifedipine mitochondrial function, but it is not known whether the oxidative stress status of the nucleus and mitochondria are differentially affected by p53. JNKs are involved in activation of caspases, but their role is not uncomplicated. JNK activation could be either upstream or downstream of cell death activation, depending on cell type and death-initiating agents. We therefore evaluated whether DOX treatment increases JNK in mitochondria as a result of 4-HNE increase, using a phospho-specific antibody that recognizes dual site phosphorylation of JNK at Thr183 and Tyr185. The best known function of p53 is its action as a transcription factor. p53 can Choline Chloride activate or suppress expression of its target genes in a number of ways. Upon exposure to various forms of stress, such as DNA damage, oncogenic activation, hypoxia, mitotic apparatus dysfunction, telomere erosion, energy stress or oxidative stress, p53 coordinates cellular responses through both transcription-dependent and -independent mechanisms. These responses prevent or repair genomic damage, or eliminate cells when damage is beyond repair. The present study identifies a novel mechanism by which p53 activation selectively enhances DOX-induced oxidative stress in mitochondria, which is manifested by an increase in the level of 4HNE-adducted proteins in the mitochondria.