Cardiolipin Mediate Curcumin Interactions with Mitochondrial Membranes

Curcumin, the main molecular ingredient of the turmeric spice, has been reported to exhibit therapeutic properties for varied diseases and pathological conditions. While curcumin appears to trigger multiple signaling pathways, the precise mechanisms for its therapeutic activity have not been deciphered. Here we show that curcumin exhibits significant interactions with cardiolipin (CL), a lipid exclusively residing in the mitochondrial membrane. Specifically, we found that curcumin significantly affected the structures and dynamics of CL-containing biomimetic mitochondrial membranes. Application of several biophysical techniques reveal that CL promotes association and internalization of curcumin into lipid bilayers. In parallel, curcumin association with CL-containing bilayers increased their fluidity and reduced lipid ordering. This investigation suggests that membrane modifications mediated by CL interactions might play a role in the therapeutic functions of curcumin, and that the inner mitochondrial membrane in general might constitute potential drug targets.