Cell death and the mitochondria: therapeutic targeting of the BCL-2 family-driven pathway
Details
Publication Year 2014-03-28, Volume 171, Issue #8, Page 1973–1987
Journal Title
British journal of pharmacology
Publication Type
Journal Article
Abstract
The principal biological role of mitochondria is to supply energy to cells, though intriguingly, evolution has bestowed another essential function upon these cellular organelles: under physiological stress, mitochondria become the cornerstone of apoptotic cell death. Specifically, mitochondrial outer-membrane permeabilization (MOMP) allows cell death factors such as cytochrome c to be released into the cytoplasm, thus inducing caspase activation and the eventual destruction of essential cellular components. The BCL-2 family proteins control the tightly regulated pathway that causes MOMP. The equilibrium between pro-survival and pro-apoptotic members of the BCL-2 family dictates the fate of cells, the homeostasis of organs, and by extension, the health of whole organisms. Dysregulation of this equilibrium is implicated in a large number of diseases such as cancer, auto-immunity and neuro-degenerative conditions. Modulating the activity of the BCL-2 family of proteins with small molecules or peptides is an attractive but challenging therapeutic goal. This review highlights the latest developments in this field and provides evidence that this strategy will likely have a positive impact on the treatment of still poorly addressed medical conditions.
Publisher
WILEY
Keywords
apoptosis;BCL-2 family;protein-protein interactions;cancer;neuro-degenerative diseases
WEHI Research Division(s)
Chemical Biology; Structural Biology
Publisher's Version
https://doi.org/10.1111/bph.12431
NHMRC Grants
NHMRC/1025138 NHMRC/1023055
ARC Grants
ARC/FT0992105,
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2014-01-17 08:17:13
Last Modified: 2015-03-24 01:36:26
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