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Ceramide Channels

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Bioactive Ceramides in Health and Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1159))

Abstract

Are ceramide molecules capable of self-assembling in biological and phospholipid membranes to form ceramide channels: membrane channels capable to translocating proteins through said membranes? A number of papers have been published which support the conclusion that ceramide forms these large channels in membranes. The evidence is extensive and consisting of: flux studies using isolated mitochondria, liposomes and planar membranes; visualization by electron microscopy; elastic deformation studies; and regulation by Bcl-2 family proteins. The evidence supports a structural model of the channel shown to be stable by molecular dynamic simulations and having structural and mechanical properties consistent with multiple experiments. Yet the novelty of this claim raises legitimate questions. Indeed, a recent report questions the existence of ceramide channels based on liposome experiments. This review presents both a comprehensive description of the major observations supporting the case that ceramide channels do exist and addresses the issues raised in the skeptical report.

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Abbreviations

MIM:

mitochondrial inner membrane

MOM:

mitochondrial outer membrane

SLs:

sphingolipids

References

  • Abou-Ghali M, Stiban J (2015) Regulation of ceramide channel formation and disassembly: insights on the initiation of apoptosis. Saudi J Biol Sci 22:760–772

    Article  CAS  Google Scholar 

  • Anishkin A, Sukharev S, Colombini M (2006) Searching for the molecular arrangement of transmembrane ceramide channels. Biophys J 90:2414–2426

    Article  CAS  Google Scholar 

  • Artetxe I, Ugarte-Uribe B, Gil D et al (2017) Does ceramide form channels? The ceramide-induced membrane permeabilization mechanism. Biophys J 113:860–868

    Article  CAS  Google Scholar 

  • Birbes H, Luberto C, Hsu YT et al (2005) A mitochondrial pool of sphingomyelin is involved in TNFalpha-induced Bax translocation to mitochondria. Biochem J 386:445–451

    Article  CAS  Google Scholar 

  • Chang K-T, Anishkin A, Patwardhan GA et al (2015) Ceramide channels: destabilization by Bcl-xL and role in apoptosis. Biochim Biophys Acta Biomembr 1848:2374–2384

    Article  CAS  Google Scholar 

  • Chanturiya A, Chernomordik LV, Zimmerberg J (1997) Flickering fusion pores comparable with initial exocytotic pores occur in protein-free phospholipid bilayers. Proc Natl Acad Sci U S A 94:14423–14428

    Article  CAS  Google Scholar 

  • Colombini M (2010) Ceramide channels and their role in mitochondria-mediated apoptosis. Biochim Biophys Acta Bioenerg 1797:1239–1244

    Article  CAS  Google Scholar 

  • Corrotte M, Almeida PE, Tam C et al (2013) Caveolae internalization repairs wounded cells and muscle fibers. Elife 2:e00926

    Article  Google Scholar 

  • Elrick MJ, Fluss S, Colombini M (2006) Sphingosine, a product of ceramide hydrolysis by ceramidase, disassembles ceramide channels. Biophys J 91:1749–1756

    Article  CAS  Google Scholar 

  • Ganesan V, Perera MN, Colombini D et al (2010) Ceramide and activated Bax act synergistically to permeabilize the mitochondrial outer membrane. Apoptosis 15:553–562

    Article  CAS  Google Scholar 

  • García-Ruiz C, Colell A, Marí M et al (1997) Direct effect of ceramide on the mitochondrial electron transport chain leads to generation of reactive oxygen species. Role of mitochondrial glutathione. J Biol Chem 272:11369–11377

    Article  Google Scholar 

  • Grassme H, Jekle A, Riehle A et al (2001) CD95 signaling via ceramide-rich membrane rafts. J Biol Chem 276:20589–20596

    Article  CAS  Google Scholar 

  • Hannun YA, Obeid LM (2011) Many ceramides. J Biol Chem 286:27855–27862

    Article  CAS  Google Scholar 

  • Hannun YA, Obeid LM (2017) Sphingolipids and their metabolism in physiology and disease. Nat Rev Mol Cell Biol 19:175–191

    Article  Google Scholar 

  • Holz R, Finkelstein A (1970) The water and nonelectrolyte permeability induced in thin lipid membranes by the polyene antibiotics nystatin and amphotericin B. J Gen Physiol 56:125–145

    Article  CAS  Google Scholar 

  • Muller RU, Finkelstein A (1972) Voltage-dependent conductance induced in thin lipid membranes by monazomycin. J Gen Physiol 60:263–284

    Article  CAS  Google Scholar 

  • Negrete H, Rivers R, Gough AH et al (1996) Individual leaflets of a membrane bilayer can independently regulate permeability. J Biol Chem 271:11627–11630

    Article  CAS  Google Scholar 

  • Perera MN, Ganesan V, Siskind LJ et al (2012a) Ceramide channels: influence of molecular structure on channel formation in membranes. Biochim Biophys Acta 1818:1291–1301

    Article  CAS  Google Scholar 

  • Perera MN, Lin SH, Peterson YK et al (2012b) BAX, Bcl-xL exert their regulation on different sites of the ceramide channel. Biochem J 445:81–91

    Article  CAS  Google Scholar 

  • Perera MN, Ganesan V, Siskind LJ et al (2016) Ceramide channel: structural basis for selective membrane targeting. Chem Phys Lipids 194:110–116

    Article  CAS  Google Scholar 

  • Samanta S, Stiban J, Maugel TK et al (2011) Visualization of ceramide channels by transmission electron microscopy. Biochim Biophys Acta 1808:1196–1201

    Article  CAS  Google Scholar 

  • Shao C, Sun B, Colombini M et al (2012) Dynamics of ceramide channels detected using a microfluidic system. PLoS One 7:e43513

    Article  CAS  Google Scholar 

  • Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 387:569–572

    Article  CAS  Google Scholar 

  • Siskind LJ, Colombini M (2000) The lipids C2- and C16-ceramide form large stable channels: implications for apoptosis. J Biol Chem 275:38640–38644

    Article  CAS  Google Scholar 

  • Siskind LJ, Kolesnick RN, Colombini M (2002) Ceramide channels increase the permeability of the mitochondrial outer membrane to small proteins. J Biol Chem 277:26796–26803

    Article  CAS  Google Scholar 

  • Siskind LJ, Davoody A, Lewin N et al (2003) Enlargement and contracture of C2-ceramide channels. Biophys J 85:1560–1575

    Article  CAS  Google Scholar 

  • Siskind LJ, Kolesnick RN, Colombini M (2006) Ceramide forms channels in mitochondrial outer membranes at physiologically relevant concentrations. Mitochondrion 6:118–125

    Article  CAS  Google Scholar 

  • Siskind LJ, Feinstein L, Yu T et al (2008) Anti-apoptotic Bcl-2 family proteins disassemble ceramide channels. J Biol Chem 283:6622–6630

    Article  CAS  Google Scholar 

  • Sot J, Goñi FM, Alonso A (2005) Molecular associations and surface-active properties of short- and long-N-acyl chain ceramides. Biochim Biophys Acta 1711:12–19

    Article  CAS  Google Scholar 

  • Stiban J, Perera M (2015) Very long chain ceramides interfere with C16-ceramide-induced channel formation: a plausible mechanism for regulating the initiation of intrinsic apoptosis. Biochim Biophys Acta 1848:561–567

    Article  CAS  Google Scholar 

  • Stiban J, Fistere D Jr, Colombini M (2006) Dihydroceramide hinders ceramide channel formation: implications on apoptosis. Apoptosis 11:773–780

    Article  CAS  Google Scholar 

  • Yamane M, Moriya S, Kokuba H (2017) Visualization of ceramide channels in lysosomes following endogenous palmitoyl-ceramide accumulation as an initial step in the induction of necrosis. Biochem Biophys Rep 11:174–181

    PubMed  PubMed Central  Google Scholar 

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Correspondence to Marco Colombini .

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Colombini, M. (2019). Ceramide Channels. In: Stiban, J. (eds) Bioactive Ceramides in Health and Disease. Advances in Experimental Medicine and Biology, vol 1159. Springer, Cham. https://doi.org/10.1007/978-3-030-21162-2_3

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