Original Article

Effect of doxorubicin on polymorphic phase transition of cardiolipin-containing membrane induced by protons

Authors: Feng-Li Zhang, Bo-Ji Cheng, Ke-Chun Lin

Abstract

Cardiolipin specific to inner mitochondrial mcmbrane is one of the lipids which can form nonbilayer phase under certain conditions. With 31P NMR, it was observed that the hexagonal II phase in cardiolipin-containing liposome membrane was formed by proton induction. Gradual lowering of pH from 7.4 to 2.0 by addition of HCl transformcd the 3lP NMR spectrum of membranc lipid from a broad asymmetric signal with high field peak and low field shoulder to a reversed asymmetric signal with high field shoulder and low field peak. The alteration in signal indicated a polymorphic phase transition of cardiolipin from bilayer to hexagonal II phase. This transition set going at pH 4.0. In the presence of doxorubicin. the induced polymorphic phase transition for cardiolipin by proton was prevent in the pH range from 5.0 to 1.5. However, at pH 0.5 the prevention was not seen due to decomposition of doxorubicin. The possible mechanism for doxorubicin to inhibit mitochondrial function is discussed.
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