The long term goal of our research is to investigate the biochemical mechanisms of redox imbalance stress and its role in adult-onset metabolic syndrome. In particular, we are studying how mitochondrial redox sensitive proteins respond to redox imbalance stress and explore such responses as potential therapeutic targets for fighting aging-related metabolic diseases. Our current projects are focused on two NADH/NAD-dependent mitochondrial proteins: dihydrolipoamide dehydrogenase (DLDH) and complex I (NADH-ubiquinone oxidoreductase), both of which can be simultaneously analyzed by blue native gel electrophoresis and also show adaptive responses to NADH/NAD redox imbalance stress under pathophysiological conditions. The DLDH project studies its adaptive response as a viable druggable target for induction of stroke- or hypoxia tolerance and the mechanisms of this protein’s oxidative modifications in redox signaling and neuroprotection. The complex I project on studies the mechanisms of complex I adaptive hyperactivity observed in diabetic pancreas and other tissues with the goal of exploring strategies that down-regulating complex I hyperactivity by restoring NADH/NAD redox balance may serve as a therapeutic approach for treating diabetes mellitus.