Ceramide channels and mitochondrial outer membrane permeability

Journal of Bioenergetics and Biomembranes
Marco Colombini

Abstract

Among the permeability pathways in the mitochondrial outer membrane (MOM), whose elucidation was pioneered by Kathleen Kinnally, there is one formed by the lipid, ceramide. Electron microscopic visualization shows that ceramide channels are large cylindrical structures of varying pore size, with a most frequent size of 10 nm in diameter, large enough to allow all soluble proteins to translocate between the cytosol and the mitochondrial intermembrane space. Similar results were obtained with electrophysiological measurements. Studies of the dynamics of the channels are consistent with a right cylinder. Ceramide channels form at mole fractions of ceramide that are found in the MOM early in the apoptotic process, before or at the time of protein release from mitochondria. That these channels are good candidates for the protein release pathway is supported by the fact that channel formation is inhibited by anti-apoptotic proteins and favored by Bax. Bcl-xL inhibits ceramide channel formation by binding to the apolar ceramide tails using its hydrophobic grove. Bax interaction with the polar regions of ceramide results in MOM permeabilization through synergy with ceramide. Evidence that ceramide channels actually function to favor ap...Continue Reading

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