Climacostol inhibits Tetrahymena motility and mitochondrial respiration

Abstract

Climacostol is a resorcinol derivative that is produced by the ciliate Climacostomum virens. Exposure to purified climacostol results in lethal damage to the predatory ciliate Dileptus margaritifer and several other ciliates. To elucidate the mechanism of climacostol toxic action, we have investigated the effects of this compound on the swimming behavior of Tetrahymena thermophila and the respiratory system of isolated rat liver mitochondria. When added to living T. thermophila cells, climacostol markedly increased the turning frequency that was accompanied by a decrease in swimming velocity and subsequently by cell death. Observations by DIC and fluorescence microscopy showed morphological alterations in climacostol treated T. thermophila, indicating that climacostol might exert cytotoxic action on this organism. In the experiment with isolated rat liver mitochondria, climacostol was found to inhibit the NAD-linked respiration, but had no apparent effect on succinate-linked respiration. This finding indicates that climacostol specifically inhibits respiratory chain complex I in mitochondria. The combination of results suggest that the inhibition of mitochondrial respiration may be the cytotoxic mechanism of climacostol’s defenses against predatory protozoa.

Chemical defence by mono-prenyl hydroquinone in a freshwater ciliate, Spirostomum ambiguum

“…With regard to the mechanism of action, euplotin C and climacostol have been shown to activate programmed cell death by impairing mitochondrial membrane potential and inducing ROS generation (Cervia et al, 2007;Buonanno et al, 2008;Muto et al, 2011). In the case of blepharismins, it was proposed that the induction of ion-permeable channel formation in cell membranes may play an important role in the defensive function of the toxins against predatory ciliates (Muto et al, 2001).…”

Simple mechanosense and response of cilia motion reveal the intrinsic habits of ciliates

“…Serial transfer of the cells was performed twice per week. Before observation, the cells in midlog phase were washed three times with observation solution [10 mM 3-(N-morpholino)propanesulfonic acid/Tris (pH 7.2), 1 mM KCl, 1 mM NaCl, and 1 mM CaCl 2 ] ( 49 ) and equilibrated with observation solution for more than 1 h before observation.…”

DNA binding and oxidative DNA damage induced by climacostol–copper(II) complexes: Implications for anticancer properties

“…Buonanno and Ortenzi [15] demonstrated that the cytotoxic potency of climacostol on free-living freshwater ciliates can be modulated by the substitution of the double bond in the aliphatic chain of the toxin with a single or a triple one. Muto et al [16,17] found that climacostol specifically inhibits respiratory chain complex I in rat liver mitochondria, inducing a consequent generation of reactive oxygen species (ROS). Finally, Buonanno et al [18] and Fiorini et al [9] observed that climacostol can inhibit the growth of human cancer cell lines in a dose-dependent manner and induce apoptosis by triggering the mitochondrial (intrinsic) pathway.…”