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Mechanisms of cytochrome c release from mitochondria

Mitochondrial outer membrane permeabilization is therefore considered a key initiative step in the apoptotic process, although the precise mechanisms regulating this event for long time remained elusive. The permeabilization of the mitochondrial outer membrane and release of intermembrane space proteins, especially, cytochrome c is unequivocally one of the central events of apoptosis.

The mechanism by which these intermembrane space proteins are released from mitochondria depends presumably on cell type and the nature of stimuli. It might include the induction of mitochondrial permeability transition, formation of specific pores by Bcl-2 family proteins, volume-dependent MPT-independent mechanisms as well as mediated by caspase-2.

The variety of mechanisms of cytochrome c release may explain diversities in the response of mitochondria to numerous apoptotic stimuli in different types of cells. Potential users of this knowledge are researchers in cell death field, oncologists developing new tools to activate cell death machinery via mitochondria and pharmaceutical industries developing specific drugs acting via mitochondria.

Reported by

Division of Toxicology, Karolinska Institutet
Nox 210, Nobels vag., 13
17177 Stockholm
Sweden
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