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Targeting mitochondrial permeability in cancer drug development
Author(s) -
Berridge Michael V.,
Herst Patries M.,
Lawen Alfons
Publication year - 2009
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.200700493
Subject(s) - mitochondrion , programmed cell death , microbiology and biotechnology , mitochondrial permeability transition pore , apoptosis , organelle , biology , cancer cell , inner mitochondrial membrane , cell , membrane permeability , mitochondrial membrane transport protein , cancer , membrane , biochemistry , genetics
The past decade has seen the emergence of a new mechanistic paradigm of cancer therapeutics. Not only have mitochondria taken centre stage as key cellular organelles mediating intrinsic pathways of cell death by apoptosis, but nonapoptotic pathways have also been shown to involve mitochondrial mechanisms. Both pathways of cell death involve permeabilization of mitochondrial membranes, but the exact nature of the molecular complexes involved at the inner mitochondrial membrane (IMM) and outer mitochondrial membrane (OMM) remains uncertain in the light of recent gene knockout studies. Consequently, the boundary between mitochondrially‐mediated apoptotic and nonapoptotic cell death is controversial. Here, we discuss the nature of the pore complexes involved in permeabilization of the IMM and OMM. Several compounds that interact directly with components of these pore complexes and have been shown to exhibit anticancer activity are discussed while other compounds appear to act indirectly through stress‐related pathways.