Mitochondrial dysfunction is currently considered one of the main causes of
multiple organ failure in chronic
inflammation and
sepsis. The participation of microbial metabolites in disorders of bioenergetic processes in mitochondria has been revealed, but their influence on the mitochondrial membrane permeability has not yet been studied. We tested the influence of various groups of microbial metabolites, including indolic and phenolic
acids,
trimethylamine-N-oxide (
TMAO) and
acetyl phosphate (AcP), on the nonspecific permeability of mitochondrial membranes under conditions of
acidosis, imbalance of
calcium ions and excess free
iron, which are inherent in
sepsis. Changes in the parameters of the
calcium-induced opening of the
mitochondrial permeability transition pore (MPTP) and
iron-activated swelling of rat liver mitochondria were evaluated. The most active metabolites were
indole-3-carboxylic acid (ICA) and
benzoic acid (BA), which activated
MPTP opening and swelling under all conditions. AcP showed the opposite effect on the induction of
MPTP opening, increasing the threshold concentration of
calcium by 1.5 times, while
TMAO activated swelling only under acidification. All the redox-dependent effects of metabolites were suppressed by the
lipid radical scavenger butyl-hydroxytoluene (
BHT), which indicates the participation of these microbial metabolites in the activation of
membrane lipid peroxidation. Thus, microbial metabolites can directly affect the nonspecific permeability of mitochondrial membranes, if conditions of
acidosis, an imbalance of
calcium ions and an excess of free
iron are created in the pathological state.