Destabilization of membranes containing cardiolipin or its precursors by peptides derived from mitogaligin, a cell death protein.
Galig, a gene embedded within the galectin-3 gene, induces cell death when transfected in human cells. This death is associated with cell shrinkage, nuclei condensation, and aggregation of mitochondria. Galig contains two different overlapping open reading frames encoding two unrelated proteins. Previous observations have shown that one of these proteins, named mitogaligin, binds to mitochondria and promotes the release of cytochrome c. However, the mechanism of action of this cytotoxic protein remains still obscure. The present study provides evidence that synthetic peptides enclosing the mitochondrial localization signal of mitogaligin bind to anionic biological membranes leading to membrane destabilization, aggregation, and content leakage of mitochondria or liposomes. This binding to anionic phospholipids is the most efficient when cardiolipin, a specific phospholipid of mitochondria, is inserted in the membranes. Thus, cardiolipin may constitute a target of choice for mitogaligin sorting and membrane destabilization activity.
Gonzalez
Patrick
P
Centre de Biophysique Moléculaire (Affiliated with the University of Orléans), CNRS UPR4301, Rue Charles Sadron, 45071 Orléans Cedex 2, France.
Duneau
Mélanie
M
Charpentier
Stéphane
S
Normand
Thierry
T
Mollet
Lucile
L
Dubois
Martine
M
Legrand
Alain
A
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001798:Blood Proteins / Q000235:genetics; D002308:Cardiolipins / Q000737:chemistry*; D016923:Cell Death / Q000235:genetics; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D037161:Galectins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D014162:Transfection
D001798:Blood Proteins; D002308:Cardiolipins; D037161:Galectins; C428445:LGALS3 protein, human; D008081:Liposomes; D010455:Peptides; D045304:Cytochromes c