Regulation of ceramide channels by Bcl-2 family proteins

Ganesan, Vidyaramanan; Colombini, Marco

doi:10.1016/j.febslet.2010.02.032

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Volume 584, Issue 10 , Pages 2128-2134, 17 May 2010

Regulation of ceramide channels by Bcl-2 family proteins

Edited by Adam Szewczyk

Department of Biology, University of Maryland, College Park, MD 20742, United States

Received 6 January 2010; received in revised form 9 February 2010; accepted 10 February 2010. published online 15 February 2010.

Abstract

Mitochondrial outer membrane permeabilization to proteins, an irreversible step in apoptosis by which critical proteins are released, is tightly regulated by Bcl-2 family proteins. The exact nature of the release pathway is still undefined. Ceramide is an important sphingolipid, involved in various cellular processes including apoptosis. Here we describe the structural properties of ceramide channels and their regulation by the anti-apoptotic and pro-apoptotic proteins of the Bcl-2 family. The evolutionarily conserved regulation of ceramide channels by Bcl-2 family proteins, consistent with their role in apoptosis, lends credibility to the notion that ceramide channels constitute the protein release pathway.

Abbreviations: MOM, mitochondrial outer membrane, ER, endoplasmic reticulum, BH, Bcl-2 homology domain

Keywords: Bax, Bcl-xL, Bid, Sphingolipid, Mitochondrion, Apoptosis