Disruption of the mitochondrial-nuclear network leads to accelerated aging and age-related diseases, including age-related macular degeneration. The current study tested the hypothesis that mitochondrial morphology could be demonstrated quantitatively using a mathematic model and mitochondrial trafficking complex under stress conditions. To test our hypothesis, normal and aberrant mitochondria were examined quantitatively based on mitochondrial size, shape, position, composition, and dynamics. Adaptation of the mitochondrial network to changes in the intracellular oxidation and reduction milieu is critical for the survival of retinal pigment epithelial cells. Our mitochondrial interactome mapping demonstrated that a positive correlation may exist between oxidative stress-mediated phosphorylation and age-related disease progression. The current interactome may provide a potential therapeutic approach to treat mitochondria-induced neurodegeneration, including age-related macular degeneration.
Part of the book: Mitochondrial Diseases
In the current study, we suggest that phosphorylation reactions of specific proteins in mitochondria and the nucleus are a key step in the progression of age-related macular degeneration (AMD). To determine the molecular mechanism of AMD, we examined proteomic changes under oxidative stress to establish the protein interaction map using in vitro and in vivo models that mimic the complex and progressive characteristics of AMD. We postulated that apoptosis can be initiated by phosphorylation reactions under chronic oxidative stress in a region-specific and tissue-specific manner. The analysis of AMD interactome and oxidative biomarker network demonstrated that the presence of tissue- and region-dependent post-translational mechanisms may contribute toward AMD progression through the mitochondrial-nuclear communication. The AMD interactome suggests that new therapeutic targets, including prohibitin, erythropoietin, vitronectin, crystalline, nitric oxide synthase, ubiquitin, and complement inhibition may exist as a proteome network. Further, immunocytochemistry demonstrated that mitochondria could enter the nucleus in the retinal pigment epithelium (RPE) under oxidative stress. The current interactome map implies that a positive correlation may exist between oxidative stress-mediated phosphorylation and AMD progression. The unbiased proteome network provides a basis for understanding oxidative stress-induced mitochondrial dysfunction in AMD and exploring effective therapeutic approaches to treat age-related neurodegeneration.
Part of the book: Visual Impairment and Blindness