Zinc as an Inducer of the Membrane Permeability Transition in Rat Liver Mitochondria

• Published in: Archives of biochemistry and biophysics 1999-03, Vol.363 (1), p.1-8
• Main Authors: Wudarczyk, Jolanta, Dębska, Grażyna, Lenartowicz, Ewa
• Format: Article
• Language: English
• Subjects: Animals; Glutathione - metabolism; Hydrogen-Ion Concentration; Intracellular Membranes - drug effects; Intracellular Membranes - metabolism; Lipid Peroxidation - drug effects; liver mitochondria; membrane permeability transition; Membrane Potentials - drug effects; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Mitochondrial Swelling - drug effects; Permeability; Rats; Thiobarbituric Acid Reactive Substances - metabolism; zinc; Zinc - pharmacology
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1006/abbi.1998.1058

It is shown that 2–10 μM Zn2+induces swelling of rat liver mitochondria incubated in a buffered sucrose medium either with valinomycin or with FCCP, Ca2+, ionophore A23187, oligomycin, and nigericin. This swelling was associated with the release of GSH from mitochondria. Both processes were sensitive to known inhibitors of the mitochondrial permeability transition (MPT), cyclosporin A, and Mg2+. Mitochondrial swelling induced by Zn2+was also inhibited by rotenone, antymycin A,N-ethylmaleimide, butylhydroxytoluene, and spermine, whereas it was stimulated bytert-butyl hydroperoxide, diamide, and monobromobimane. It did not require the addition of phosphate. The same sensitivity to pH of the mitochondrial swelling induced by Zn2+and by phenylarsine oxide suggests the same site of the interaction, namely, thiol groups. The ability of Zn2+to induce mitochondrial swelling gradually decreased along with its increasing concentration above 10 μM. It is concluded that micromolar Zn2+induces the MPT presumably by the interaction with cysteinyl residues. This process is independent of the mitochondrial membrane potential.