The mitochondrial gateway to cell death

IUBMB Life
Danielle J SmithPhillip Nagley

Abstract

Mitochondria play a key role in death signaling. The intermembrane space of these organelles contains a number of proteins which promote cell death once they are redistributed to the cytosol. The formation of pores in the outer membrane of mitochondria defines a gateway through which the apoptogenic proteins pass during death signaling. Interactions between pro-apoptotic and pro-survival members of the Bcl-2 family of proteins are decisive in the initiation of pore opening. While the specific composition of the pore in molecular terms is still subject to debate and continuing investigation, it is recognized functionally as a passive channel which not only allows egress of proteins to cytosol but also entry in the reverse direction. A variety of constraints may restrict the release of proteins from the intermembrane space to the cytosol. These include trapping in the intercristal spaces formed by the convoluted invaginations of the inner membrane, binding of proteins to the inner membrane or to other soluble proteins of the intermembrane space, or insertion of proteins into the inner membrane. There is a corresponding variety of mechanisms that facilitate release of apoptogenic proteins from such entrapment. Morphological change...Continue Reading

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