Targeting mitochondria for cancer therapy

被引:1381
作者
Fulda, Simone [2 ]
Galluzzi, Lorenzo [1 ,3 ,4 ]
Kroemer, Guido [1 ,3 ,4 ]
机构
[1] Inst Gustave Roussy, INSERM, U848, French Med Res Council, F-94805 Villejuif, France
[2] Univ Ulm, Univ Childrens Hosp, D-89075 Ulm, Germany
[3] Inst Gustave Roussy, PR1, F-94805 Villejuif, France
[4] Univ Paris 11, F-94805 Villejuif, France
关键词
BH3 MIMETIC ABT-737; PERIPHERAL BENZODIAZEPINE-RECEPTOR; PERMEABILITY TRANSITION PORE; PHASE-I TRIAL; BCL-2 ANTISENSE OLIGONUCLEOTIDE; ADENINE-NUCLEOTIDE TRANSLOCASE; ALPHA-TOCOPHERYL SUCCINATE; CELL-LUNG-CANCER; OUTER-MEMBRANE PERMEABILIZATION; MYELOGENOUS LEUKEMIA STEM;
D O I
10.1038/nrd3137
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Mitochondria are the cells' powerhouse, but also their suicidal weapon store. Dozens of lethal signal transduction pathways converge on mitochondria to cause the permeabilization of the mitochondrial outer membrane, leading to the cytosolic release of pro-apoptotic proteins and to the impairment of the bioenergetic functions of mitochondria. The mitochondrial metabolism of cancer cells is deregulated owing to the use of glycolytic intermediates, which are normally destined for oxidative phosphorylation, in anabolic reactions. Activation of the cell death machinery in cancer cells by inhibiting tumour-specific alterations of the mitochondrial metabolism or by stimulating mitochondrial membrane permeabilization could therefore be promising therapeutic approaches.
引用
收藏
页码:447 / 464
页数:18
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