The Human Bcl-2 Family Member Bcl-rambo Localizes to Mitochondria and Induces Apoptosis and Morphological Aberrations in Drosophila

• Published in: PloS one Vol. 11; no. 6; p. e0157823
• Main Authors: Nakazawa, Mako, Matsubara, Hisanori, Matsushita, Yuka, Watanabe, Megumi, Vo, Nicole, Yoshida, Hideki, Yamaguchi, Masamitsu, Kataoka, Takao
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.06.2016; Public Library of Science (PLoS)
• Subjects: Adenine; Animals; Apoptosis; Autophagy; Autophagy-Related Protein 8 Family - genetics; Bcl-2 protein; Biology; Biology and Life Sciences; Cell cycle; Cell Line; Cytochrome; Drosophila; Drosophila melanogaster; Drosophila melanogaster - genetics; Drosophila melanogaster - growth & development; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Ectopic expression; Epistasis, Genetic; Eye; Genetic aspects; Homology; Humans; Imaginal discs; Inhibitor of Apoptosis Proteins - genetics; Inhibitor of Apoptosis Proteins - metabolism; Insects; Mammals; Medicine and Health Sciences; Mitochondria; Mitochondria - metabolism; Mitochondrial ADP, ATP Translocases - genetics; Mitochondrial DNA; Morphology; Penicillin; Phagocytosis; Phenotype; Phenotypes; Physiological aspects; Protein Transport; Proteins; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Research and Analysis Methods; Signal transduction; Signaling; Thorax; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0157823

Bcl-2 family proteins play a central role in regulating apoptosis. We previously reported that human Bcl-rambo, also termed BCL2L13, localized to mitochondria and induced apoptosis when overexpressed in human embryonic kidney 293T cells. However, the physiological function of Bcl-rambo currently remains unclear. In the present study, human Bcl-rambo was ectopically expressed in Drosophila melanogaster. Bcl-rambo mainly localized to the mitochondria of Drosophila Schneider 2 (S2) cells. The overexpression of Bcl-rambo, but not Bcl-rambo lacking a C-terminal transmembrane domain, induced apoptosis in S2 cells. Moreover, the ectopic expression of Bcl-rambo by a GAL4-UAS system induced aberrant morphological changes characterized by atrophied wing, split thorax, and rough eye phenotypes. Bcl-rambo induced the activation of effector caspases in eye imaginal discs. The rough eye phenotype induced by Bcl-rambo was partly rescued by the co-expression of p35, Diap1, and Diap2. By using this Drosophila model, we showed that human Bcl-rambo interacted genetically with Drosophila homologues of adenine nucleotide translocators and the autophagy-related 8 protein. The results of the present study demonstrated that human Bcl-rambo localized to mitochondria and at least regulated an apoptosis signaling pathway in Drosophila.