Determination of mitochondrial metabolic phenotype through investigation of the intrinsic inhibition of succinate dehydrogenase

Many diseases are accompanied by systemic or organ metabolic abnormalities. Therefore, investigation of the roles of mitochondrial dysfunction in the pathogenesis of major diseases requires a methodology that reflects the characteristics of mitochondrial metabolism particular for the organ of origin. We provide evidence that for brain and heart mitochondria the intrinsic inhibition of succinate dehydrogenase (SDH) is a key mechanism for attenuation of mitochondrial respiration and energy production in response to the organ's energy needs. This mechanism also serves to minimize the production of reactive oxygen species when the organ is at rest. Changes in the organ's workloads are accompanied by changes in metabolites that are used by mitochondria as substrates and for modification of energy production at the SDH level. Measurement of the respiratory activity of mitochondria with various substrates and substrate mixtures and use of bovine serum albumin as an SDH inhibitor will be useful for evaluation of metabolic phenotype at the mitochondrial level.