Loss of dE2F Compromises Mitochondrial Function

被引:28
作者
Ambrus, Aaron M. [1 ]
Islam, Abul B. M. M. K. [2 ,3 ]
Holmes, Katherine B. [1 ]
Moon, Nam Sung [4 ]
Lopez-Bigas, Nuria [2 ,5 ]
Benevolenskaya, Elizaveta V. [1 ]
Frolov, Maxim V. [1 ]
机构
[1] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA
[2] Univ Pompeu Fabra, Res Unit Biomed Informat, Dept Expt & Hlth Sci, Barcelona 08003, Spain
[3] Univ Dhaka, Dept Genet Engn & Biotechnol, Dhaka 1000, Bangladesh
[4] McGill Univ, Dept Biol, Montreal, PQ H3A 1B1, Canada
[5] ICREA, Barcelona 08010, Spain
基金
美国国家卫生研究院;
关键词
CELL-DEATH; TRANSCRIPTIONAL PROGRAM; S PHASE; APOPTOSIS; EXPRESSION; GENES; RB; PROLIFERATION; PROGRESSION; REPRESSION;
D O I
10.1016/j.devcel.2013.10.002
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
E2F/DP transcription factors regulate cell proliferation and apoptosis. Here, we investigated the mechanism of the resistance of Drosophila dDP mutants to irradiation-induced apoptosis. Contrary to the prevailing view, this is not due to an inability to induce the apoptotic transcriptional program, because we show that this program is induced; rather, this is due to a mitochondrial dysfunction of dDP mutants. We attribute this defect to E2F/DP-dependent control of expression of mitochondria-associated genes. Genetic attenuation of several of these E2F/DP targets mimics the dDP mutant mitochondrial phenotype and protects against irradiation-induced apoptosis. Significantly, the role of E2F/DP in the regulation of mitochondrial function is conserved between flies and humans. Thus, our results uncover a role of E2F/DP in the regulation of mitochondrial function and demonstrate that this aspect of E2F regulation is critical for the normal induction of apoptosis in response to irradiation.
引用
收藏
页码:438 / 451
页数:14
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