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Targeting mitochondria for cancer therapy

2010; Nature Portfolio; Volume: 9; Issue: 6 Linguagem: Inglês

10.1038/nrd3137

1474-1784

Simone Fulda, Lorenzo Galluzzi, Guido Kroemer,

ATP Synthase and ATPases Research

The key roles of mitochondria in energy production and the regulation of apoptosis are frequently deregulated in cancer. Attempts to activate the cell death machinery in cancer cells by inhibiting tumour-specific alterations of the mitochondrial metabolism or by stimulating mitochondrial membrane permeabilization, could represent a promising strategy for the treatment of cancer. 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.