The energy-producing mitochondria are central to maintenance and survival of cells and have been proposed to participate in the pathogenesis of organ dysfunction. We use sensitive systems for analysis of mitochondrial function and have developed high-resolved respirometry applied to human blood cells. With this rapid and easy accessible method to monitor systemic mitochondrial function we determine bioenergetic capacity in children presenting with idiopathic encephalopathy or suspected mitochondrial disease, patients with chronic neurodegenerative disorders and patients with sepsis, conditions in which mitochondrial dysfunction has been implicated in the pathogenesis. An additional goal is to identify and move to clinical application pharmaceutical agents that can preserve or enhance mitochondrial function. For this purpose we have, in collaboration with industry, developed novel mitochondrial energy substrates and a porcine model of mitochondrial disease/acute metabolic decompensation.