Microtubule-active drugs suppress the closure of the permeability transition pore in tumour mitochondria.

We report the effects of anticancer drugs, inhibitors of microtubule organisation, on the mitochondrial permeability transition pore (PTP) in Ehrlich ascites tumour cells. Taxol (5-20 microM) and colchicine (100-500 microM) prevented closing of the cyclosporin A-sensitive PTP. No taxol or colchicine effects on oxidative phosphorylation were observed in the range of concentrations used. We suggest that either membrane-bound tubulin per se can be part of PTP and/or the attachment of mitochondria to the microtubular network is essential for PTP regulation. The taxol inhibition of PTP closure, mediated through interaction with the cytoskeleton, sheds new light on the cytotoxic properties of this anticancer drug.

[Redistribution of Ca2+ ions in Ehrlich ascites carcinoma cells under the action of deoxyglucose and inhibitors of the intracellular Ca2+- transporting system]. / Pereraspredelenie ionov Ca2+ v kletkakh astsitnoi kartsinomy Erlikha pod deistviem dezoksigliukozy i ingibitorov vnutrikletochnykh Ca2+-transportiruiushchikh sistem.

Changes in free cytoplasmic Ca2+ ([Ca2+]i) in Ehrlich ascites tumour cells were studied under the effect of deoxyglucose and agents which modify transmembrane Ca2+ fluxes. It was shown that the reason for deoxyglucose-induced [Ca2+]i increase in Ca2+ release from internal stores and the influx from the external medium. Mitochondrial metabolic inhibitors (oligomycin+KCN, oligomycin++uncouplers of oxidative phosphorylation) induce themselves some rise in [Ca2+]i and increase the deoxyglucose effect on [Ca2+]i significantly. The conclusion was made that mitochondria can participate in cytosolic Ca2+ regulation and Ca2+ redistribution in tumour cells.

[Characteristics of reversible and irreversible Ca2+-induced efflux of Ca2+ from mitochondria in permeabilized Ehrlich ascites carcinoma cells]. / Kharakteristiki obratimogo i neobratimogo Ca2+-indutsirovannogo vykhoda Ca2+ iz mitokhondrii permeabilizirovannykh kletok astsitnoi kartsinomy Erlikha.

The Cyclosporin A-sensitive mitochondrial permeability transition in Ehrlich ascites tumour cells has been investigated. It was shown that Ca2+ ions induce both the self-reversible and irreversible mitochondrial permeability transition. ADP effectively inhibits the reversible but has no effect on the irreversible permeability transition. Bromophenacyl bromide, a potent inhibitor of phospholipase A2, effectively inhibits both the reversible and irreversible permeability transition. Accumulation of phosphatidylcholine and phosphatidylethanolamine lysoforms in mitochondria during Ca(2+)-induced Ca2+ release from mitochondria was found. The role of lysophospholipids in the formation of the non-selective pore in inner mitochondrial membranes during the mitochondrial permeability transition was postulated.

Mitochondrial calcium spiking: a transduction mechanism based on calcium-induced permeability transition involved in cell calcium signalling.

We report reversible Ca(2+)-induced Ca2+ release from mitochondria, which takes the form of Ca2+ spikes. Mitochondrial Ca2+ spiking is an all-or-none process with a threshold dependence on both the frequency and the amplitude of the Ca2+ pulses used as stimuli. This spiking relies on the transient operation of the mitochondrial permeability transition pore, and is initiated--in a threshold-dependent manner--with inositol-triphosphate-mediated Ca2+ responses on permeabilized cells. Evidence that mitochondrial Ca(2+)-induced Ca2+ release contributes to inositol-triphosphate-mediated Ca2+ responses in intact cells is also reported.

[Character and reasons for change in mitochondrial ATP content during auto-oscillation of ion currents]. / Kharakter i prichiny izmeneniyia soderzhaniia ATP v mitokhondriiakh v khode avtokolebanii ionnykh potokov.

The changes in the adenosine triphosphate content in the course of ionic flux oscillations in mitochondria were estimated by using the chemiluminescence method. The ATP concentration changes were shown to be of cyclic character; the oscillations in the ATP content were shifted by 180 degrees C against those of K+ fluxes. The oligomycin-induced oxidative phosphorylation blocking changed (but did not eliminate) the oscillational character of the ATP content in mitochondrial suspensions. It was concluded that substrate phosphorylation is the source of ATP under conditions of oxidative phosphorylation inhibition. Incubation of mitochondria in the presence of exogenous ATP led to suppression of ionic flux oscillations.