Tl(III) interaction with cardiolipin alters membrane physical properties and cytochrome c binding

PUGA MOLINA, L. C.; VERSTRAETEN, S. V.

Mar del Plata, Buenos Aires, Argentina

Congreso; XLIII Reunión Annual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2007

SAIB

Trivalent thallium (Tl(III)) is highly toxic to humans through not well understood mechanisms. In PC12 cells, we demonstrated that Tl(III) causes mitochondrial dysfunction and cell apoptosis. In the present study, we evaluated the effects of Tl(III) (5-75 M) on cardiolipin (CL)-containing membranes physical properties, and how cytochrome c binding to CL is affected. Working with PC:CL liposomes (80:20 molar ratio) we found that after 1 h of incubation at 37ºC, no Tl(III) was bound to membranes, since it was reduced to Tl(I). Accordingly, a significant oxidative damage to both fatty acids and CL polar headgroup was observed. Immediately after Tl(III) addition, liposome membrane surface potential, fluidity and hydration were significantly decreased, and CL pKa decreased from 10.1 to 8.6. The magnitude of Tl(III)- mediated membrane rigidification and dehydration was even higher after 1 h of incubation. Cytochrome c binding to CL was significantly impaired in liposomes incubated for 1 h in the presence of Tl(III). Present results indicate that Tl(III) significantly affect the physical properties of CL-containing membranes, altering cytochrome c binding to CL. These deleterious effects of Tl(III) could be partially involved in mitochondrial dysfunction in cells exposed to this metal. This work was supported with grants from UBA (B072) and CONICET(PIP 5536), Argentina.