title: The Drosophila retinoblastoma protein, Rbf1, induces a Debcl- and Drp1-dependent mitochondrial apoptosis.
abstract: In accordance with its tumor suppressor role, the retinoblastoma protein pRb can ensure pro-apoptotic functions. Rbf1, the Drosophila homolog of Rb, also displays a pro-apoptotic activity in proliferative cells. We have previously shown that the Rbf1 pro-apoptotic activity depends on its ability to decrease the level of anti-apoptotic proteins such as the Bcl-2 family protein Buffy. Buffy often acts in an opposite manner to Debcl, the other Drosophila Bcl-2-family protein. Both proteins can localize at the mitochondrion, but the way they control apoptosis still remains unclear. Here, we demonstrate that Debcl and the pro-fission gene Drp1 are necessary downstream of Buffy to trigger a mitochondrial fragmentation during Rbf1-induced apoptosis. Interestingly, Rbf1-induced apoptosis leads to a Debcl- and Drp1-dependent reactive oxygen species production, which in turn activates the Jun Kinase pathway to trigger cell death. Moreover, we show that Debcl and Drp1 can interact and that Buffy inhibits this interaction. Notably, Debcl modulates Drp1 mitochondrial localization during apoptosis. These results provide a mechanism by which Drosophila Bcl-2 family proteins can control apoptosis, and shed light on a link between Rbf1 and mitochondrial dynamics in vivo.
authors.affiliation: Université de Versailles Saint-Quentin-en-Yvelines, Laboratoire de Génétique et Biologie Cellulaire, EA4589, 2 avenue de la Source de la Bièvre, Montigny-le-Bretonneux 78180, France Ecole Pratique des Hautes Etudes, Laboratoire de Génétique et Biologie Cellulaire, 2 avenue de la Source de la Bièvre, Montigny-le-Bretonneux 78180, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Clavier
authors.affiliation: Université de Versailles Saint-Quentin-en-Yvelines, Laboratoire de Génétique et Biologie Cellulaire, EA4589, 2 avenue de la Source de la Bièvre, Montigny-le-Bretonneux 78180, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Ruby
authors.affiliation: Université de Versailles Saint-Quentin-en-Yvelines, Laboratoire de Génétique et Biologie Cellulaire, EA4589, 2 avenue de la Source de la Bièvre, Montigny-le-Bretonneux 78180, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Rincheval-Arnold
authors.affiliation: Université de Versailles Saint-Quentin-en-Yvelines, Laboratoire de Génétique et Biologie Cellulaire, EA4589, 2 avenue de la Source de la Bièvre, Montigny-le-Bretonneux 78180, France Ecole Pratique des Hautes Etudes, Laboratoire de Génétique et Biologie Cellulaire, 2 avenue de la Source de la Bièvre, Montigny-le-Bretonneux 78180, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Mignotte
authors.affiliation: Université de Versailles Saint-Quentin-en-Yvelines, Laboratoire de Génétique et Biologie Cellulaire, EA4589, 2 avenue de la Source de la Bièvre, Montigny-le-Bretonneux 78180, France isabelle.guenal@uvsq.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Guénal
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C477358:Buffy protein, Drosophila; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C099965:Rbf protein, Drosophila; D016160:Retinoblastoma Protein; D014157:Transcription Factors; C404322:debcl protein, Drosophila; C504426:DRP1 protein, Drosophila; D019204:GTP-Binding Proteins
keywords: Apoptosis; Debcl; Drp1; Mitochondrial dynamics; Rbf1