Maspin binds to cardiolipin in mitochondria and triggers apoptosis

What is it about?

This manuscript describes an exciting biochemical discovery underlying the mitochondrial regulation of apoptosis. We demonstrate that the serine protease inhibitor, maspin, binds tightly to cardiolipin in the inner mitochondrial membrane (IMM) and is connected to the release of membrane-bound cytochrome c and initiation of apoptosis. Our in vivo and in vitro biochemical analyses indicate a 27-amino acid hydrophobic, lysine-rich domain in maspin mediates its interaction with cardiolipin. Altering maspin's cardiolipin-binding domain inhibits its affinity for the membrane and decreases cytochrome c release and apoptosis in tumor cells._x000D_ _x000D_ The successful treatment of cells desensitized to apoptotic signaling remains a challenge in cancer chemotherapies. Insight into the essential relationship between peripheral membrane proteins (i.e., cytochrome c, maspin, tBid, Bax, and others) and the inner mitochondrial membrane may reveal design principles for effective chemotherapeutic strategies. This study takes a step toward this goal by providing insight into the relationship between maspin, cytochrome c, and cardiolipin in the inner mitochondrial membrane and its connection to apoptosis.

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