Format

Send to

Choose Destination
J Cell Sci. 2015 Sep 1;128(17):3239-49. doi: 10.1242/jcs.169896. Epub 2015 Jul 24.

The Drosophila retinoblastoma protein, Rbf1, induces a Debcl- and Drp1-dependent mitochondrial apoptosis.

Author information

1
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.
2
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.
3
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.

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.

KEYWORDS:

Apoptosis; Debcl; Drp1; Mitochondrial dynamics; Rbf1

PMID:
26208635
DOI:
10.1242/jcs.169896
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center