Structural and functional changes in rat liver mitochondria under calcium ion loading in the absence and presence of flavonoids

Abstract

The aim of the present work was to elucidate the mechanisms of calcium ion-induced impairments of the ultrastructure and functional activity of isolated rat liver mitochondria in the absence and presence of a number of flavonoids in vitro. In the presence of exogenous Ca2+ (20-60 μM), mitochondrial heterogeneity in size and electron density markedly increased: most organelles demonstrated a swollen electron-light matrix, bigger size, elongated cristae and a reduced their number, a damaged native structure of the inner membrane up to its detachment, and some mitochondria showed a more electron-dense matrix (condensed mitochondria). The calcium-induced opening of the mitochondrial permeability transition pores (MPTP) resulted in the ultrastructural disturbances and in the effective inhibition of the respiratory activity of rat liver mitochondria. The flavonoids (10-25 μM) naringenin and catechin, dose-dependently inhibited the respiratory activity of mitochondria and stimulated the MPTP opening in the presence of Ca2+ ions. Since Ruthenium red, an inhibitor of the mitochondrial Ca2+ uniporter, effectively prevented Ca2+-induced MPTP opening both in the absence and presence of flavonoids, we hypothesized that the effect of flavonoids on the MPTP opening could be mediated by stimulation of the Ca2+ uniporter.