Journal
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
Volume 72, Issue -, Pages 152-162Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcdb.2017.04.001
Keywords
Apoptosis; BCL-2 family proteins; Mitochondrial outer membrane; permeabilisation; BAK; BAX; Oligomers
Categories
Funding
- NHMRC [1059331, 1079706, 1079700]
- Victorian State Government
- National Health and Medical Research Council of Australia [1079706, 1079700, 1059331] Funding Source: NHMRC
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Apoptosis is a form of programmed cell death critical for the development and homeostasis of multicellular organisms. A key event within the mitochondrial pathway to apoptosis is the permeabilisation of the mitochondrial outer membrane (MOM), a point of no return in apoptotic progression. This event is governed by a complex interplay of interactions between BCL-2 family members. Here we discuss the roles of opposing factions within the family. We focus on the structural details of these interactions, how they promote or prevent apoptosis and recent developments towards understanding the conformational changes of BAK and BAX that lead to MOM permeabilisation. These interactions and structural insights are of particular interest for drug discovery, as highlighted by the development of therapeutics that target pro-survival family members and restore apoptosis in cancer cells. Crown Copyright (C) 2017 Published by Elsevier Ltd. All rights reserved.
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