hFis1, a novel component of the mammalian mitochondrial fission machinery.
The balance between the fission and fusion mechanisms regulate the morphology of mitochondria. In this study we have identified a mammalian protein that we call hFis1, which is the orthologue of the yeast Fis1p known to participate in yeast mitochondrial division. hFis1, when overexpressed in various cell types, localized to the outer mitochondrial membrane and induced mitochondrial fission. This event was inhibited by a dominant negative mutant of Drp1 (Drp1(K38A)), a major component of the fission apparatus. Fragmentation of the mitochondrial network by hFis1 was followed by the release of cytochrome c and ultimately apoptosis. Bcl-xL was able to block cytochrome c release and apoptosis but failed to prevent mitochondrial fragmentation. Our studies show that hFis1 is part of the mammalian fission machinery and suggest that regulation of the fission processes might be involved in apoptotic mechanisms.
James
Dominic I
DI
Department of Cell Biology, University of Geneva, Quai Ernest-Ansermet 30, 1211 Geneva, Switzerland.
Parone
Philippe A
PA
Mattenberger
Yves
Y
Martinou
Jean-Claude
JC
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000378:metabolism; D019556:COS Cells; D002460:Cell Line; D002470:Cell Survival; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D005799:Genes, Dominant; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008565:Membrane Proteins; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions; D014162:Transfection; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D001426:Bacterial Proteins; C476525:FIS1 protein, human; D008164:Luminescent Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; C054562:yellow fluorescent protein, Bacteria; D045304:Cytochromes c; D008156:Luciferases