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The effect of DDT on K+ transport in mouse liver mitochondria
Abstract:
This study describes DDT-induced changes in membrane permeability of mitochondria and erythrocytes to K+ as monitored by a K+-selective electrode. DDT is a strong inhibitor of valinomycin-mediated K+ uptake and the corresponding H+ efflux and an inducer of K+ leakage out of mitochondria but not to any significant extent out of erythrocytes. The inhibition of K+ uptake and H+ efflux was a function of (a) preincubation time between mitochondria and DDT, (b) mitochondrial concentration, (c) the nature of the carrier solvent and (d) temperature. The kinetics of inhibition of K+ uptake showed that DDT is an uncompetitive inhibitor with respect to valinomycin and a competitive inhibitor with respect to K+. The efflux of endogenous K+ showed a sigmoid dependency on DDT concentration and was reduced to endogenous rates when the temperature was lowered below the gel-liquid crystalline phase transition of the lipids. It is suggested that the DDT-induced changes in membrane permeability are due to perturbation of the lipid phase and that its toxicity may be due in part to hyperpolarization of subcellular membranes.
Insights
DDT disrupts mitochondrial membrane permeability to potassium (K+), inhibiting uptake and inducing leakage. These effects, linked to lipid phase perturbation, may contribute to DDT
Area of Science:
- Biochemistry
- Toxicology
- Cell Biology
Background:
- Mitochondria and erythrocytes are key cellular components involved in ion transport.
- DDT (dichlorodiphenyltrichloroethane) is an organochlorine pesticide with known toxic effects.
- Membrane permeability is crucial for cellular function and homeostasis.
Purpose of the Study:
- To investigate DDT's effects on potassium (K+) permeability in mitochondria and erythrocytes.
- To elucidate the mechanisms underlying DDT-induced alterations in membrane transport.
- To explore the relationship between DDT, lipid phase transitions, and cellular toxicity.
Main Methods:
- Utilized a K+-selective electrode to monitor K+ flux across mitochondrial and erythrocyte membranes.
- Assessed DDT's impact on valinomycin-mediated K+ uptake and H+ efflux.
- Analyzed the kinetics of K+ uptake inhibition and endogenous K+ efflux under varying conditions (preincubation time, concentration, temperature, solvent).
Main Results:
- DDT strongly inhibited valinomycin-mediated K+ uptake and H+ efflux in mitochondria.
- DDT induced significant K+ leakage from mitochondria but not erythrocytes.
- Inhibition kinetics revealed DDT as an uncompetitive inhibitor to valinomycin and competitive to K+.
- Endogenous K+ efflux exhibited a sigmoid dependency on DDT concentration and was temperature-dependent, linked to lipid phase transitions.
Conclusions:
- DDT-induced changes in membrane permeability are likely caused by perturbation of the mitochondrial lipid phase.
- DDT's toxicity may be partly attributed to the hyperpolarization of subcellular membranes.
- Differential effects on mitochondria versus erythrocytes highlight specific cellular targets of DDT.