AbstractMitochondrial dysfunction is the main factor in the development of multiple organ failure in sepsis. The role of microbial metabolites in the induction of mitochondrial dysfunction was studied in this work. The effect of phenolic acids of microbial origin on the functions of mitochondria in acidosis and deficiency of the substrate of oxidation accompanying the development of sepsis was investigated. These conditions considerably enhanced the effects of benzoic, phenylpropanoic, phenylpropionic, and phenylacetic acids on the induction of the mitochondrial pore, oxidation of NADH, and oxidative phosphorylation in isolated liver mitochondria. The deficiency of the substrate of oxidation was the most effective factor that enhanced the effect of phenolic acids. Preincubation of mitochondria with phenolic acids in the absence of the substrate of oxidation was accompanied by a significant inhibition of the dehydrogenases of the tricarboxylic acid cycle. The obtained data indicate a potential role of phenolic acids of microbial origin in the development of mitochondrial dysfunction in inflammation and sepsis.